An investigation into the serum thioredoxin, superoxide dismutase, malondialdehyde, and advanced oxidation protein products in patients with breast cancer.

BACKGROUND: Reactive oxygen species (free radicals) play an important role in carcinogenesis. Extensive antioxidant defense mechanisms counteract free radicals in mammalian cells. Oxidative stress is a disturbance in the balance between the production of free radicals and antioxidant defenses. There is direct evidence that oxidative stress and lipid peroxidation (LPO) are linked to the etiology of breast cancer. The increasing global incidence of breast cancer emphasizes the need to understand the various mechanisms involved in breast tumorigenesis. The present study was undertaken to investigate the oxidative stress and antioxidant status in the blood samples of patients with breast cancer. METHODS: The present study was based on 23 women who were surgically treated at Gazi University, Faculty of Medicine, Department of General Surgery. The malondialdehyde (MDA) levels as an index of LPO along with the examination of superoxide dismutase (SOD) activities and advanced oxidation protein product (AOPP) and thioredoxin (Trx) levels were determined in the blood samples of 23 patients with breast cancer and 13 healthy controls. RESULTS: MDA, AOPP, and Trx levels and SOD activities were significantly higher in patients with breast cancer than the controls. CONCLUSIONS: The results showed that oxidative stress may be related to breast cancer and especially some molecules, such as Trx and AOPP, may be useful biomarkers in breast cancer diagnosis and treatment. More detailed knowledge related to the pathophysiology of these molecules could provide valuable information on the origin and development of malignant tumors, such as breast cancer.

Phyllodes tumor of the breast; a case series.

BACKGROUND: Phyllodes tumor (PT) is a rare neoplasm comprising less than 1% of all breast tumors. Its clinical spectrum ranges from a benign and locally recurrent form of behavior to malignant and metastatic forms. The aim of the study was to evaluate the clinical characteristics, treatment regimens, survival and late complications in patients with PT. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 10 women who were treated for PT in our center between 1998 and 2002. All cases were histologically examined by an experienced breast pathologist, and tumors were classified as benign, borderline malignant or malignant according to standard histological criteria. RESULTS: The median age at diagnosis was 45.5 years (range: 21-69 years). Seven (70%) of 10 tumors were benign and 3 (30%) were malignant. The median tumor size was 29 mm (range: 12-80 mm). The least safe margin was 1 cm. Three of 10 patients had malignant PT and underwent simple mastectomy. Local recurrence was determined in no patients. Only one patient had lung metastasis. Median follow-up period was 62 months (range, 12-96 months). The patient with lung metastasis was treated with doxorubicine but died one year after the operation. CONCLUSION: PT is a rare neoplasm of the breast. It resembles fibroadenoma. Local excision with appropriate surgical margins seems adequate in all patients (Tab. 1, Fig. 3, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

The value of breast ductoscopy in radiologically negative spontaneous/persistent nipple discharge.

Breast ductoscope is a fiberoptic endoscope used for examining the distal breast ducts under direct vision in order to identify the source of pathologic nipple discharge. The purpose of this study was to investigate the reliability of intra-operative breast ductoscopy in patients with pathologic nipple discharge, which could not be identified by radiologic tests. Between April 2002 and March 2007, breast ductoscopy was performed in 34 patients who had pathologic nipple discharge with no radiologic evidence about the source. The procedures were carried out under general anesthesia and ductoscopic findings were as well as the histopathology of the specimens were recorded and documented. In 88%, (30 of 34) of the patients, endoscope was successfully introduced into the external orifice of the ducts at the nipple and proximal breast ducts were successfully visualized. Ductoscopy revealed intraductal lesions (i.e., ductal obstruction, intraductal papilloma, red patches, and erythematoid platter) in 20 patients (66%). Among the 20 patients with visible endoluminal pathology, nine had a papilloma and eight had signs of either acute inflammation (bleeding, erythema) or previous inflammation with healing (adhesions and blocked ducts). In two cases, invasive breast carcinoma was identified, one of which was ductal carcinoma in situ (DCIS) with minimal invasion. In both cases, there had been blocked ducts. In one case DCIS was identified. Breast ductoscopy is a reliable and easy-to-use method to demonstrate the source of pathologic nipple discharge in cases with bleeding and other intraductal lesions.

Immune system modulation in patients with malignant and benign breast disorders: tryptophan degradation and serum neopterin.

Tryptophan degradation metabolites are known to suppress T-cell function, which is a mechanism of resistance of tumor cells against immune surveillance. The aim of this study was to evaluate tryptophan degradation along with serum neopterin levels in benign and malignant breast disease. Serum tryptophan and kynurenine levels and neopterin concentrations of 30 patients with malignant and 27 patients with benign breast disease were determined by HPLC and ELISA, respectively. The slight increase in tryptophan degradation in a subgroup of cancer patients with higher grade tumors was not statistically significant, but the increased degradation was correlated with higher neopterin concentrations. Neopterin levels in patients with malignant breast disease were significantly higher than in the benign group (p<0.05). Tryptophan degradation positively correlates with the aggressiveness of the tumor because it changes with tumor grade rather than disease stage.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer.

INTRODUCTION: YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer. METHODS: YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths. RESULTS: The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 microg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05). CONCLUSION: Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

Single nucleotide polymorphisms in the hypoxia-inducible factor-1alpha (HIF-1alpha) gene in human sporadic breast cancer.

BACKGROUND: DNA sequence variations in hypoxia-inducible factor-1alpha (HIF-1alpha) gene, which have been demonstrated to be correlated with tumor angiogenesis, may yield changes both in the production outcomes and in the activities of the gene. In this study, we investigated the relationship between three single nucleotide polymorphisms (SNPs) [C1772T and G1790A in exon 12 and C111A in exon 2 of the HIF-1alpha gene] in the HIF-1alpha gene coding regions and development of sporadic breast cancer in the Turkish population. These three polymorphisms result in an amino acid change from proline 582 to serine, from alanine 588 to threonine and from serine 28 to tyrosine, respectively. METHODS: Genomic DNA was isolated from 102 sporadic breast cancer patients and 102 healthy female controls. All three HIF-1alpha gene regions were amplified by PCR, and genotypes were determined by RFLP and DNA sequencing. RESULTS: There were no significant differences between patients and controls in terms of the distribution of C1772T and G1790A polymorphisms of HIF-1 gene (p >0.05). As for HIF-1alpha C111A polymorphism, we did not find CA and AA variants of the gene in either controls or patients. Multivariable logistic regression analysis was performed between CC and CT + TT genotypes of C1772T polymorphism. No significant differences were found between these two genotypes in terms of clinicopathological characteristics of the patients including age at enrollment, age at menarche and first delivery, number of full-term pregnancies, body mass index, use of oral contraceptives and postmenopausal hormones, family history of breast and ovarian cancers, menopausal status, histopathological features, oophorectomy, smoking habits, and alcohol consumption (p >0.05). CONCLUSIONS: Our results suggest that none of the polymorphisms studied in the HIF-1alpha gene influence susceptibility to sporadic breast cancer. The present study is the first case-control study that investigates the association of HIF-1alpha polymorphisms with sporadic breast cancer in the Turkish population.

Microanatomy of milk ducts in the nipple.

The aim of this study was to determine number and diameter of milk ducts in the nipple and to investigate the possible influences of age, breast weight, and diameter of the nipple on the number of ducts. Two hundred and twenty-six carcinoma mastectomy specimens were weighed and the nipple diameters measured. The number of ducts was counted in histological cross sections. Mean diameter of the nipple and mean breast weight were 13.9 mm and 844.6 g, respectively. There was a small but statistically significant positive correlation between nipple diameter and number of milk ducts (rho = 0.158; p = 0.01), but no correlation with breast weight. The mean number of ducts in the nipple duct bundle was 17.5. This is significantly higher than the number of ducts reported to open on the nipple surface. This discrepancy could reflect duct branching within the nipple or the presence of some ducts which do not reach the nipple surface. Smaller breast ducts (diameter < 0.5 mm) represent nearly 50% of the nipple ducts and could be a challenge to the ductoscopy technology.

The effects of carbon dioxide pneumoperitoneum on tyrosine hydroxylase activity.

PURPOSE: The aim of this study is to investigate the effects of carbon dioxide (CO2) pneumoperitoneum on tyrosine hydroxylase (TH) activity and total protein (TP) levels. METHODS: Forty male Sprague-Dawley rats were randomized into 10 groups, each consisting of 10 rats. Groups 1 and 2 consisted of anesthesia and sham-operated control rats, respectively. In the study groups, 10 mm Hg (group 3) and 15 mm Hg (group 4) pneumoperitoneum with CO2 were accomplished. At the end of the procedures, the brains and adrenals were removed quickly, and the hypothalamus and adrenal medulla separated, weighed, and homogenized. TH activity and TP levels were determined. RESULTS: The adrenal medulla TP and TH activity levels were decreased consistently and this decrease was significant in the sham and pneumoperitoneum groups compared with the control group (P<0.05). The adrenal medulla TP and TH activity levels were reduced significantly in group 4, as compared with the other groups (P<0.05). Elevation of hypothalamic TH activity in group 4 was significantly higher than in the other groups (P<0.05). CONCLUSIONS: These results indicate that CO2 pneumoperitoneum applied with 10 and 15 mm Hg pressure gradually decreases the adrenal medulla TH activity; TH is an indispensable enzyme for the biosynthesis of catecholamines. CO2 pneumoperitoneum with 15 mm Hg pressure significantly elevated hypothalamus TH activity.

Prospective analysis of 518 cases with thyroidectomy in Turkey.

OBJECTIVE: Thyroid malignancies can present in different manners, among them as asymptomatic solid nodule being the most puzzling. Nodules have been found in the 60-70 % of autopsy specimens and it is very important to rule out the malignancies in such cases. Incidence of carcinomatous changes is reported in 5-15 % of solitary nodules. We present the results of prospective study on 418 thyroidectomies with the aim to review the experience of our unit, to establish the correlation between clinical presentation and histopathology, to discuss the malignancy rates and surgical complications. PATIENTS AND METHODS: Five hundred eighteen consecutive cases of thyroidectomy 419 female (80.8 %), and 99 male (19.2 %) patients performed between January 2002 and October 2004 were included in this prospective study. RESULTS: In 71 (13.7 %) cases the malignancy was found by paraffin specimens, the highest prevalence of malignancy being found in patients with nodular goiter (NG-18 %) followed by 14.6 % in multinodular goiter (MNG). The sensitivity of preoperative fine needle cytology (FNAC) was 83.3 % with false positive rate of 1.3 %. Complications were seen in 5.2 % of cases of which 4 (0.7 %) had hypoparathyroidism and 7 (1.3 %) had recurrent laryngeal nerve injury. All patients observed came from endemic area. Family history nearly doubles the risk of malignancy. CONCLUSIONS: In an endemic area the nodular goiter is the most common. Preoperative cytology, although sensitive, gives a considerable number of false positive results. Results of thyroid surgery at a high volume centre are satisfactory with very low rates of recurrent laryngeal nerve and parathyroid injury. Probability of malignant transformation in a long standing thyroid swelling should always be kept in mind. There appears to be an increase in prevalence of thyroid malignancies in Turkey after Chernobyl disaster.

Clinical presentation and treatment of hyperthyroidism associated with thyroid cancer.

OBJECTIVE: Hyperthyroidism apparently does not protect the patients from thyroid cancer as believed before. In contrast, hyperthyroidism with concurrent thyroid cancer can be diagnosed after pathological examination of unsuspect nodules. The aim of this study was to evaluate the coexistence of hyperthyroidism and thyroid carcinoma and to discuss the advantages of total thyroidectomy in such cases. METHODS: Between January 2002 and October 2004, 120 hyperthyroid patients underwent surgical treatment in our clinic. All patients with hyperthyroidism in this study underwent fine-needle aspiration biopsy and cytologic examination. Frozen section evaluation was performed in all of these patients during the operation. RESULTS: Among these patients 10 had concurrent thyroid cancer. Only one of these patients was examined by fine needle aspiration biopsy prior to operation, while the rest of malignancies was diagnosed from unsuspect nodules. CONCLUSIONS: The selection of appropriate operation procedure appears very important to find out and treat concurrent thyroid cancers. We diagnosed 90 % of thyroid cancers incidentally. If there are no technical difficulties, we prefer total thyroidectomy for the patients with toxic multinodular goiter and Graves' disease with nodules.

Laparoscopic "second-look" in the management of mesenteric ischemia.

Mesenteric ischemia is a major cause of mortality in surgery. Despite the advances in medicine, considerable number of patients undergoes reoperations for a better assessment of intestinal viability. Although great majority of these second-look operations are "negative explorations," progressive nature of this devastating disease pushes surgeons to re-explore the abdomen. This study compares open and laparoscopic "second-look" procedures in patients with mesenteric ischemia. In the first group (n = 41), abdomen was closed and second-look laparotomy was performed to 23 patients. In the second group (n = 36), a 10-mm trocar was inserted before closing the abdomen and second-look intervention was performed by a telescope to 23 patients. Sixteen of relaparotomies in the first group (70%) revealed nothing and were unnecessary. Two patients (8%) in the laparoscopy group needed re-resection while 20 patients (87%) were rescued from unnecessary laparotomies. Conclusively, patients with mesenteric ischemia are "ill enough" to deserve the "minimal invasion" spirit of laparoscopic surgery.

Outcome and cost comparison of laparoscopic transabdominal preperitoneal hernia repair versus Open Lichtenstein technique.

Laparoscopic hernia repair has all the advantages of a tension free repair. This study compares the laparoscopic transabdominal preperitoneal (TAPP) approach with tension-free open hernia repair in terms of operative time, postoperative pain, hospital stay, complications, and cost. Open and TAPP repairs using polypropylene mesh were performed in two groups of 25 male patients. The difference in operative times between the groups was not significant. Mean pain scores (0-100) for the open group were 54.12 +/- 13.06 at 12 hours and 37.24 +/- 11.38 at 24 hours, significantly higher than the corresponding scores of 38.36 +/- 8.21 at 12 hours and 20.92 +/- 8.73 at 24 hours for the TAPP group (P < 0.05). The mean postoperative analgesic dose was 6.72 +/- 2.72 in the TAPP group, which was insignificantly lower than 7.52 +/- 2.00 in the open group. Mean hospital stay was 2.24 +/- 0.97 days in the open group and 1.52 +/- 0.51 in the TAPP group, which was significant (P < 0.05). Twenty patients (80%) in the TAPP group rated themselves highly satisfied with the surgery as compared to 11 patients (44%) in the open group (P < 0.05). There was no recurrence in either group during a mean followup period of 13.5 months (range, 8-28 months). Laparoscopic hernia repair was significantly more expensive than open (1100 US dollars versus 629 US dollars). TAPP repair is superior to open repair in terms of shorter hospital stay, lower postoperative pain, and better patient satisfaction. It is also safe, with no recurrence in a short-term period. This technique will be the operation of choice for the treatment of groin hernia after long-term results have been established in our center.