Prognostic significance of EGFR and COX-2 expression in colorectal cancer and their association. A study in Greek population.

PURPOSE: Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population. METHODS: Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department. We examined patient age, sex, tumor stage and location of the tumor. Histological data were also retrieved concerning major tumor diameter, histological grade and immunohistochemical expression of cyclooxygenase (COX)-2 and epithermal growth factor receptor (EGFR). RESULTS: There was no difference between tumors of different differentiation in the expression of EGFR (p=0.146), while there was statistically significant difference in the expression of COX-2 between these groups (p=0.001). There was no difference between these patients in the expression of EGFR (p=0.136), while a statistically significant difference was found in the expression of COX-2 between the same patient groups (p<0.005). CONCLUSION: These data are quite important in order to certify that colorectal cancer molecular and genetic diversity between different study populations is not a confounding factor in the application and clinical implementation of trending individualized decision making in oncological treatments.

Does internal stenting of the pancreaticojejunostomy improve outcomes after pancreatoduodenectomy? A prospective study.

AIM: This study's aim is to evaluate the effectiveness of using an internal stent when fashioning a duct-to-mucosa pancreatojejunostomy on preventing pancreatic fistula formation, as well as on the overall outcome for patients undergoing pancreaticoduodenectomy. MATERIALS AND METHODS: Between January 2000 and December 2008, 82 consecutive patients underwent pancreaticoduodenectomy and duct-to-mucosa pancreaticojejunostomy in an isolated jejunal loop, either with or without the aid of an internal stent. The allocation of the patients into group A (n = 41, stented anastomosis) and group B (n = 1, unstented anastomosis) was performed in a strictly alternating way. No statistically significant differences were identified between the two groups regarding age, sex, operative time, intraoperative pathological findings, and comorbidities. The two groups were compared regarding the rate of pancreatic fistula formation, postoperative complications, and hospital stay. RESULTS: In group A, pancreatic fistula formation rate was 4.9%; overall morbidity reached 30%; and hospital stay duration was 13 +/-4 days. In group B, pancreatic fistula formation rate was 2.4%; overall morbidity was 26%; and hospital stay duration extended to 14 +/- 5. According to Clavien's classification, the severity of surgical complications was designated as follows: for group A, 56% of the complications were allocated as grade I, 38% grade II, 4% grade III, 2.5% grade IV, and 0% grade V. The relative values for group B were 53%, 42%, 3%, 2%, and 0%, respectively. In six group A patients (14.7%), the internal stent was found stuck in the pancreatic stump, causing severe back pain requiring analgesic treatment with opioids for four of them. In group B, four patients (9.7%) complained of mild back pain, none of which required regular treatment. No mortalities were recorded in both groups. No statistically significant differences were found between the two groups regarding fistula formation and severity of complications. CONCLUSIONS: Internal stenting of a duct-to-mucosa pancreatojejunostomy does not diminish the rate of pancreatic fistula formation or alter overall patient's outcome.

Expression of c-kit in common benign and malignant breast lesions.

AIMS AND BACKGROUND: c-kit (CD117) is a transmembrane tyrosine kinase that acts as a type III receptor for mast cell growth factor. In recent years, the role of c-kit in the development of preinvasive and invasive breast carcinomas has been investigated. The aim of our study was to detect c-kit expression in the entire spectrum of common benign and malignant breast lesions in correlation with a well-studied myoepithelial or stem-cell like marker (p63). METHODS AND STUDY DESIGN: We evaluated 270 cases of benign and malignant breast lesions including fibrocystic disease, fibroadenoma, sclerosing adenosis, atypical ductal hyperplasia, ductal/lobular carcinoma in situ, and ductal/lobular/mixed type carcinoma. C-kit staining was evaluated in the cytoplasm/cell membrane in epithelial and myoepithelial cells and p63 in the nuclei of myoepithelial cells. RESULTS: c-kit was highly expressed (85.3%) in benign lesions (fibrocystic disease, sclerosing adenosis, fibroadenoma), and p63 expression was 95.5% in the aforementioned lesions. c-kit distribution in preinvasive and invasive lesions was as follows: ductal/lobular carcinoma in-situ, 43%/35%; ductal/lobular carcinoma, 36%/39%; and mixed type carcinoma, 20%. c-kit was highly expressed in myofibroblast/fibroblast cells only in grade III ductal/lobular carcinomas. c-kit was totally absent in stromal cells in benign lesions and in situ carcinomas whereas expression was weak in grade I and II carcinomas. CONCLUSIONS: Combined overexpression of c-kit and p63 is indicative of benign breast lesions. In contrast, there is reduced expression of c-kit in in situ and invasive breast carcinomas, with simultaneous overexpression in the stromal cells. This suggests that c-kit may play a role in breast cancer progression.

Abnormal uterine bleeding as a presentation of metastatic breast disease in a patient with advanced breast cancer.

BACKGROUND: Extragenital carcinomas secondarily involving the uterus are very rare and they usually occur as a manifestation of widespread disease. When the metastases involve the endometrium in a diffuse, permeative pattern, sparing the glands, they may cause problems in the diagnosis. CASE: A case of metastatic carcinoma to the endometrium with a decidua-like pattern is reported. The patient had a history of breast carcinoma and presented with vaginal bleeding. The pathologic findings in the uterine curettings raised the differential diagnosis between metastatic breast carcinoma and non-neoplastic stromal lesions. The presence of nuclear atypia and mitotic activity along with the appropriate immunohistochemical findings revealed the neoplastic nature of the endometrial lesion and confirmed its origin from the breast. CONCLUSION: Unusual uterine bleeding in a patient with breast cancer should alert the gynecologist to the possibility of metastatic breast disease. Furthermore, the metastasis to the uterus and to other organs of the genital tract can be considered as a preterminal event.

Genetic polymorphisms in the UGT1A1 gene and breast cancer risk in Greek women.

Uridine diphospho-glucuronosyltransferase 1 (UGT1A1) is involved in estradiol glucuronidation, which may play a central role in the etiology of breast cancer. A common insertion/deletion polymorphism in the TATAA-box of the promoter region of UGT1A1 results in decreased initiation of transcription, and has been associated with breast cancer risk in different ethnic groups. In the present study, the role of the above genetic variation at the UGT1A1 locus in breast cancer susceptibility was investigated in a homogeneous population. Our case-control study included 136 women with breast cancer and 186 healthy female controls of Greek origin. The polymorphism A(TA)nTAA in the promoter region of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7, and normal homozygous 6/6) were identified. No significant associations were observed between the 7/7 genotype and breast cancer risk, indicating that further studies in Caucasian women are needed to elucidate the role of UGT1A1 polymorphism in breast cancer risk.

Surgical approaches of resectable synchronous colorectal liver metastases: timing considerations.

AIM: To compare the safety and efficacy of simultaneous versus two stage resection of primary colorectal tumors and liver metastases. METHODS: From January 1996 to May 2004, 103 colorectal tumor patients presented with synchronous liver metastases. Twenty five underwent simultaneous colorectal and liver surgery and 78 underwent liver surgery 1-3 mo after primary colorectal tumor resection. Data were retrospectively analyzed to assess and compare the morbidity and mortality between the surgical strategies. The two groups were comparable regarding the age and sex distribution, the types of liver resection and stage of primary tumors, as well as the number and size of liver metastases. RESULTS: In two-stage procedures more transfusions were required (4 +/- 1.5 vs 2 +/- 1.8, pRBCs, P < 0.05). Chest infection was increased after the two-stage approach (26% vs 17%, P < 0.05). The two-stage procedure was also associated with longer hospitalization (20 +/- 8 vs 12 +/- 6 d, P < 0.05). Five year survival in both groups was similar (28% vs 31%). No hospital mortality occurred in our series. CONCLUSION: Synchronous colorectal liver metastases can be safely treated simultaneously with the primary tumor. Liver resection should be prioritized over colon resection. It is advisable that complex liver resections with marginal liver residual volume should be dealt with at a later stage.

A phase III study of 5-fluorouracil versus 5-fluorouracil plus interferon alpha 2b versus 5-fluorouracil plus leucovorin in patients with advanced colorectal cancer: a Hellenic Cooperative Oncology Group (HeCOG) study.

We conducted a phase III study in patients with advanced colorectal carcinoma (ACC). The total number of patients randomized from October 1993 until July 1998 was 192, whereas therapy was started on 179 and 158 (82.3%) have been evaluable. The treatment schedules consisted of weekly bolus administration for 6 weeks of 5-fluorouracil (5-FU), 600 mg/m2 (arm I) versus 5-FU (500 mg/m2) intravenous bolus and interferon-alpha, 5 MU subcutaneously, three times a week (arm II) versus leucovorin 200 mg/m2 in 2-hour infusion and 5-FU 500 mg/m2 intravenous bolus at the midtime of leucovorin infusion (arm III) followed by a 2-week rest period. Treatment was continued for six cycles or until progression. This study failed to show any superiority of the modulated 5-FU versus single administration of 5-FU. There were no significant differences between the three arms in the overall response rate (10.3% versus 11.3% versus 12.9%, p = 0.95), the time to tumor progression (median, 3.9 versus 3.8 versus 6.0 months, p = 0.59), or survival duration (median, 14.7 versus 12.4 versus 16.3 months, p = 0.71). The incidence of severe (grades III and IV) toxicity was significantly higher in patients in arm II and III (24.5% and 18.6%) versus arm I (6.0%) (p = 0.01). Because modulated 5-FU failed to show superiority versus 5-FU, new agents and new strategies are needed for the treatment of advanced colorectal carcinoma.