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Dimitris D Tsiftsis

Publications and source records attributed to Dimitris D Tsiftsis.

17 recordsLinked to original sources
PubMed2007

Short-term exposure of cancer cells to micromolar doses of paclitaxel, with or without hyperthermia, induces long-term inhibition of cell proliferation and cell death in vitro.

BACKGROUND: During intraoperative hyperthermic intraperitoneal chemotherapy for primary or secondary peritoneal malignancies, tumor cells are exposed to high drug concentrations for a relatively short period of time. We investigated in vitro the effect of paclitaxel and hyperthermia on cell proliferation, cell cycle kinetics and cell death under conditions resembling those during intraoperative hyperthermic intraperitoneal chemotherapy. METHODS: Human breast MCF-7, ovarian SKOV-3 and hepatocarcinoma HEpG2 cells were exposed to 10 and 20 microM paclitaxel at 37, 41.5 or 43 degrees C for 2 h. Cell proliferation, cell cycle kinetics, necrosis and apoptosis were evaluated. RESULTS: Hyperthermia exerted a cytostatic effect to all cell lines and at 43 degrees C a cytotoxic effect on MCF-7 cells. MCF-7 and SKOV-3 cells treated under normothermic conditions with paclitaxel were arrested at G2/M or M phase for at least 3 days. Most of MCF-7 cells and approximately half of SKOV-3 cells were in interphase and became multinucleated without properly completing cytokinesis. Hyperthermia at 41.5 degrees C altered cell cycle distribution and affected the paclitaxel-related effect on cell cycle kinetics of MCF-7 and SKOV-3 cells. Analysis of the mode of cell death showed that cell necrosis prevailed over apoptosis. Hyperthermia at 43 degrees C increased paclitaxel-mediated cytotoxicity in MCF-7 cells and to a lesser extent in SKOV-3 and HEpG2 cells. CONCLUSIONS: Short-time treatment of carcinoma cells with high (micromolar) concentrations of paclitaxel in normothermic and hyperthermic conditions is highly efficient for cell growth arrest and could be of clinical relevance in locoregional chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Treatment of ovarian cancer using intraperitoneal chemotherapy with taxanes: from laboratory bench to bedside.

The combination of a taxane, paclitaxel or docetaxel, and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer and has demonstrated high efficacy. However, ultimately most patients will die from this disease. Hence, there is a need for even more effective systemic chemotherapy or different treatment strategies. Intraperitoneal chemotherapy with taxanes is such an alternative treatment option. Ovarian cancer is theoretically an attractive malignancy for this regional treatment, because the disease remains largely confined to the peritoneal cavity. The choice of taxanes for this kind of chemotherapy is rational, because of its high activity against ovarian cancer cells and expected favourable pharmacokinetics because of limited absorption from the peritoneal cavity due to their large molecular weight and first-pass effect in the liver. In animal model and human pharmacokinetic studies, very high intraperitoneal drug concentrations and exposure and high peritoneal tumour concentrations were achieved, while systemic drug levels were low. The combination of intraperitoneal chemotherapy with hyperthermia enhances the penetration and cytotoxic activity of many drugs. Although data concerning thermal enhancement of taxane cytotoxicity are inconsistent, experimental studies show that at high locoregional concentrations there seems to be such an effect. Recently, feasibility and efficacy of this treatment have evidently been demonstrated in various clinical studies. A large randomized trial revealed improvement of outcome by intraperitoneal instillation chemotherapy with paclitaxel and cisplatin as first-line treatment. Moreover, promising results have been observed after intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel for recurrent disease.

Animals↗
PubMed2006

A simple digital image processing system to aid in melanoma diagnosis in an everyday melanocytic skin lesion unit: a preliminary report.

BACKGROUND: For early melanoma diagnosis, experienced dermatologists have an accuracy of 64-80% using clinical diagnostic criteria, usually the ABCD rule, while automated melanoma diagnosis systems are still considered to be experimental and serve as adjuncts to the naked-eye expert prediction. In an attempt to aid in early melanoma diagnosis, we developed an image processing program with the aim to discriminate melanoma from melanocytic nevi, establishing a mathematical model to come up with a melanoma probability. METHODS: Digital images of 132 melanocytic skin lesions (23 melanomas and 109 melanocytic nevi) were studied in features of geometry, color, and color texture. A total of 43 variables were studied for all lesions, e.g., geometry, color texture, sharpness of border, and color variables. Univariate logistic regression analysis followed by "-2 log likelihood" test and Spearman's rank correlation coefficient were used to eliminate inappropriate variables, as the presence of multi-collinearity among variables could cause severe problems in any stepwise variable selection method. Initially, "-2 log likelihood" and nonparametric Spearman's rho picked five variables to be included in a multivariate model of prediction. The five-variable model was then reduced to three variables and the performance of each model was tested. The "jackknife" method was performed in order to validate the model with the three variables and its accuracy was weighed vs. the five-variable model by receiver-operating characteristics (ROC) curve plotting. It was concluded that the reduced model did not compromise discriminatory power. RESULTS: Not all variables contributed much to the model, therefore they were progressively eliminated and the model was finally reduced to three covariates of significance. A predictive equation was calculated, incorporating parameters of geometry, color, and color texture as independent covariates for the prediction of melanoma. The proposed model provides melanoma probability with a 60.9% sensitivity and 95.4% specificity of prediction, an overall accuracy of 89.4% (probability level 0.5), and 8% false-negative results. CONCLUSIONS: Through a digital image processing system and the development of a mathematical model of prediction, discrimination between melanomas and melanocytic nevi seems feasible with a high rate of accuracy using multivariate logistic regression analysis. The proposed model is an alternative method to aid in early melanoma diagnosis. Expensive and sophisticated equipment is not required and it can be easily implemented in a reasonably priced portable programmable computer, in order to predict previously undiagnosed skin melanoma before histopathology results confirm diagnosis.

Algorithms↗
PubMed2005

Preoperative epoetin alfa in colorectal surgery: a randomized, controlled study.

BACKGROUND: Colorectal cancer patients are often anemic before surgery, and this leads to an increased requirement for allogeneic blood transfusion. This may result in transfusion-induced immunosuppression, which in turn leads to increased morbidity and possibly an increased rate of tumor relapse. We investigated the possible benefits of perioperative epoetin alfa administration in anemic patients to correct hemoglobin levels and reduce transfusion needs. METHODS: A total of 223 colorectal cancer patients with anemia scheduled for surgery were randomized to a group that received epoetin alfa 150 or 300 IU/kg/day subcutaneously for 12 days (day -10 to +1) or to a control group. All received iron (200 mg/day by mouth) for 10 days before surgery. Hemoglobin levels, hematocrit, and the number of blood units transfused were recorded. RESULTS: A total of 204 patients were eligible for analysis. Mean hemoglobin levels and hematocrit were significantly higher in the 300 IU/kg group than in the control group, both 1 day before surgery (hemoglobin, P = .008; hematocrit, P = .0005) and 1 day after surgery (hemoglobin, P = .011; hematocrit, P = .0008). Blood loss during and after surgery was similar in all groups. Patients who received epoetin alfa 300 IU/kg required significantly fewer perioperative transfusion units than control patients (.81 vs. 1.32; P = .016) and significantly fewer postoperative units (.87 vs. 1.33; P = .023). There were no significant differences in the number of units in the 150 IU/kg group. CONCLUSIONS: Preoperative epoetin alfa (300 IU/day) increases hemoglobin levels and hematocrit in colorectal surgery patients. These effects are associated with a reduced need for perioperative and postoperative transfusions.

Adult↗
PubMed2005

Correlation of breast cancer risk factors with HER-2/neu protein overexpression according to menopausal and estrogen receptor status.

BACKGROUND: Several researchers have claimed that classification of tumours on the basis of HER-2/neu overexpression or amplification may define a subset of breast cancer in which the net effect of a risk factor could be rather more obvious and its impact on breast cancer development more clear. We decided to investigate, in a group of patients from a geographical area with a low incidence of breast cancer, whether HER-2/neu positive tumours are correlated with established or suspected risk factors for breast cancer and thus to identify distinct subgroups of high risk women. METHODS: This study analysed data from patients who attended the Breast Unit at the University Hospital of Heraklion, Crete, Greece between 1996 and 2002. 384 women with primary invasive breast cancer were compared with 566 screened women who were referred to the Unit and had not developed breast neoplasm by the time the data were analysed. Risk factor data were obtained from each subject by personal interviews using a structured questionnaire. The detection and scoring of the HER-2/neu protein, estrogen and progesterone receptor expression were performed using immunochemistry. Odds ratios and 95% confidence intervals were determined by chi-square test and logistic regression analysis. Case-case odds ratios were calculated in order to measure the risk heterogeneity between HER-2/neu+ and HER-2/neu-tumours. Separate analyses were performed for premenopausal and postmenopausal women and according to estrogen receptor status. RESULTS: In multivariate analysis without HER-2/neu stratification, an increased breast cancer risk was associated with only four of the factors examined: use of oral contraceptives (OR = 4.40, 95%C.I: 1.46-13.28), use of HRT (OR = 7.34, 95%C.I: 2.03-26.53), an age at first full pregnancy more than 23 years (OR = 1.91, 95%C.I: 1.29-2.83) and body mass index more than 29 kg/m2 (OR = 3.13, 95%C.I: 2.02-4.84). Additionally, a history of abortion or miscarriage (OR = 0.56, 95%C.I: 0.38-0.82) was correlated with a decreased risk of breast cancer. In the case to case comparison only BMI >29 kg/m2 revealed a relative connection that was stronger with positive than with negative HER-2/neu tumours (ratio of OR's = 2.23, 95%C.I: 1.20-4.15, p = 0.011). This may indicate evidence of heterogeneity of a rather significant degree for this factor. In the ER negative group an age at first full pregnancy >23 years and a BMI >29 kg/m2 were associated with an increased risk in both HER-2/neu groups, but the association was significantly stronger for the latter factor in the positive HER-2/neu tumours (ratio of OR's = 2.46, 95%CI: 0.97-6.21). CONCLUSIONS: Our study did not confirm that the established or putative hormonal breast cancer risk factors differ regarding their relations with HER-2/neu+ versus HER-2/neu-breast tumours, with the exception of increased BMI. Further innovative studies with larger sample sizes are needed to examine how the status of these potentially modifiable breast cancer risk factors interacts with biological markers such as HER-2/neu oncoprotein.

Journal Article↗
PubMed2003

How many cases are enough for accreditation in sentinel lymph node biopsy in breast cancer?

BACKGROUND: There is considerable argument concerning the number of sentinel node biopsy cases with axillary dissection that surgeons should perform before they are eligible on abandoning axillary dissection in negative sentinel node patients. DATA SOURCES: Papers that (1) address directly or indirectly the subject of credentialing or of learning curve, (2) report on a surgeon's performance, (3) are reported as feasibility or learning curve studies, or both, (4) discuss the learning curve issue, and (5) express an expert's opinion on the learning curve. CONCLUSIONS: The number of procedures of the learning curve can not be fixed for all surgeons. Only surgeons in specialized breast cancer centers can succeed in meeting current recommendations with 20 to 30 cases. Surgeons from affiliated community hospitals will need more than 30 cases, whereas broad-based surgeons might need as many as 60 cases with their current caseload. Not all surgeons will be able to offer the procedure to their patients by the current recommendations.

Accreditation↗
PubMed2003

Pharmacokinetic study of docetaxel in intraoperative hyperthermic i.p. chemotherapy for ovarian cancer.

The purpose of this study was to evaluate the pharmacokinetics and toxicity of docetaxel in continuous hyperthermic perfusion peritoneal chemotherapy (CHPPC) after cytoreductive surgery for peritoneal involvement of gynecological malignancies, mainly ovarian cancer. Eighteen patients, with a mean age of 64 years (range 51-80), underwent cytoreductive surgery and subsequent CHPPC with 75 mg/m2 docetaxel at 41-43 degrees C. One patient was treated twice. In eight cases, peritoneal fluid and blood samples were obtained for pharmacokinetic analysis. Death occurred in two heavily pretreated elderly patients with a high volume i.p. tumor recurrence, probably reflecting poor patient selection (mortality rate 10.5%). Other complications, mainly minor, were recorded after 63% of the procedures. Hematological docetaxel-induced toxicity was limited, while the incidence of wound complications was relatively high and probably caused by the direct exposure of the wound to docetaxel during CHPPC. The maximal i.p. versus plasma concentration ratio ranged from 17 to 95 (average 45), while the i.p. versus systemic exposure ratio varied between 105 and 555 (average 207). We conclude that the use of docetaxel in CHPPC following cytoreductive surgery seems feasible and results in a high i.p. versus systemic exposure ratio. The AUC for the peritoneal cavity is on average 13-27 times higher after i.p. administration of 75 mg/m2 during CHPPC than the AUC achieved in the systemic compartment after i.v. administration of the recommended dose of 100 mg/m2, while docetaxel-induced systemic toxicity is highly limited.

Aged↗
PubMed2003

Technical modification of laparoscopic vertical banded gastroplasty.

BACKGROUND: Technical improvements of laparoscopic bariatric procedures are important to minimize operative time and increase safety and simplicity. METHODS: A modification is described of the "classic" Mason-MacLean vertical banded gastroplasty (VBG), performed by laparoscopy, with wedge resection of the gastric fundus, thus avoiding the time-consuming and technically difficult gastro-gastrostomy window. RESULTS: The technique used was simple and safe, and required less operative time than the "classic" method, without serious intra- or postoperative complications. Weight loss in 18 patients who underwent the modified laparoscopic VBG and were followed-up for 1 year was equal to that achieved in patients who underwent open VBG at our Institution. Gastro-gastric fistula was not observed in upper GI barium studies performed 12 months postoperatively. CONCLUSION: The modified technique is preferable when lap-VBG is indicated for surgical treatment of morbidly obese patients.

Gastroplasty↗
PubMed2002

Secretory carcinoma of the male breast.

BACKGROUND: Secretory carcinoma is a distinctive and rare variant of breast carcinoma with a favorable prognosis because these tumors usually behave in an indolent manner. The occurrence of this type of breast cancer in males was studied. METHODS: An extensive literature survey concerning secretory breast cancer in males was performed. Data of one case treated in our institute were added. RESULTS: A total of 14 cases were identified, and our case was added to this series. The median age was 17 years. The duration of symptoms varied from 1 month to 21 years, and the tumor size was 1.2 to 4 cm. Surgical treatment varied from local excision only to modified radical mastectomy. Three patients received adjuvant treatment. Lymph nodes were involved in 3 of the 10 cases undergoing axillary lymph node dissection. The primary tumor was only 1.5 cm in diameter in two of those cases. None of the patients presented with systemic metastases. Only one male was reported to develop recurrence and consequently died of systemic disease. CONCLUSIONS: Secretory breast cancer is very rare in males and seems to occur at a younger age in males than in females. A sufficient number of female cases have been reported with recurrence after local excision. Although in females lymph node metastases are rarely observed in secretory breast carcinoma smaller than 2 cm, in male patients nodal metastases might occur more frequently in smaller tumors. Therefore, mastectomy with sentinel lymph node biopsy or axillary lymph node dissection is recommended in any male case. Biological behavior seems to be similarly favorable in either sex.

Adolescent↗
PubMedDate not supplied

Synchronous parathyroid and papillary thyroid carcinoma: a case report.

An extremely rare case of synchronous parathyroid and papillary thyroid carcinoma is reported for a patient presenting with hyperparathyroidism. This case is the first reported in the English literature of hyperfunctioning parathyroid carcinoma and concomitant thyroid carcinoma without a previous history of neck irradiation.

Carcinoma, Papillary↗
PubMedDate not supplied

Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel as second-line treatment for peritoneal carcinomatosis of gynaecological origin.

BACKGROUND: Cytoreductive surgery with continuous hyperthermic perfusion peritoneal chemotherapy (CHPPC) is a relatively new multimodality treatment for peritoneal malignancies. We studied the feasibility and outcome of CHPPC with docetaxel as second-line treatment for gynaecological peritoneal carcinomatosis. PATIENTS AND METHODS: Twenty times CHPPC with docetaxel was performed in 19 patients, mean age of 65 years (47-80), who demonstrated early recurrent or persistent peritoneal carcinomatosis mainly of ovarian origin. RESULTS: Treatment-related death was noted in 2 elderly patients with a high tumour load. Two other major complications, requiring re-operation, were recorded. Haematological docetaxel-induced toxicity was highly limited, while the wound complication rate was relatively high. Ascites disappeared in all patients. After a mean follow-up of 30 months, the actuarial overall 1- and 3-year survival rates after CHPPC were 79% and 63%. CONCLUSION: CHPPC with docetaxel following cytoreductive surgery for early recurrent or persistent peritoneal carcinomatosis from gynaecological malignancies seems feasible and might have a positive impact on survival. The outcome seems to be superior to that of CHPPC with other drugs.

Aged↗