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Biomedical subjects

Eelco de Bree

Publications and source records attributed to Eelco de Bree.

At least 19 recordsLinked to original sources

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↗

High risk of colostomy with primary radiotherapy for anal cancer.

BACKGROUND: Radiotherapy (RT) has become the primary treatment of choice for anal cancer in an effort to avoid colostomy. The current role of surgery appears generally to be underestimated, since diverting colostomy or abdominoperineal resection still often seems to be necessary for complications and local treatment failure after RT. METHODS: The data of 83 patients primarily treated by RT with curative intent throughout a 20-year period in our institute were analyzed regarding the need for colostomy. RESULTS: Totally, 28 patients (34%) required creation of a colostomy after primary RT for local failure or treatment-related complications during a mean follow-up period of 39 months. The 3-year actuarial colostomy-free rate was 59% (mean 85 +/- 9 months). Early stage disease, low T-score and absence of infiltration in adjacent organs were associated with a reduced need for colostomy in univariate analysis. In multivariate analysis only T-score was an independent variable in predicting prolonged colostomy-free interval. In this study, no statistically significant differences were noted for gender, age, nodal status, total radiation dose, radiation boost and concurrent chemotherapy. CONCLUSIONS: In approximately one-third of the patients treated by anal sphincter saving management with curative aimed primary RT, the creation of a colostomy appeared to be necessary for RT complications and local treatment failure. Therefore, patients should be well informed regarding the considerable risk of need for colostomy after RT for anal cancer.

Adult↗

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↗

Peritoneal carcinomatosis from colorectal or appendiceal origin: correlation of preoperative CT with intraoperative findings and evaluation of interobserver agreement.

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer, it is important to diagnose peritoneal carcinomatosis as well as to detect location and size of peritoneal tumor dissemination in view of treatment planning. The aim of this study was to investigate the detection accuracy of computed tomography (CT). METHODS: Preoperative CT-scans from 25 consecutive patients with peritoneal carcinomatosis from colorectal or appendiceal origin were independently blindly reviewed by 2 radiologists. The presence and diameter of tumor deposits were noted in seven abdominopelvic areas. Intraoperative findings were regarded as the gold standard. Agreement was assessed using the Kappa index and the chi-square test. RESULTS: The presence of peritoneal carcinomatosis was detected in 60 and 76% of those patients by each of the radiologist. Detection of individual peritoneal implants was poor (kappa = 0.11/0.23) and varied from 9.1%/24.3% for tumor size <1 cm to 59.3%/66.7% for tumor size >5 cm. Overall sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) for tumor involvement per area were 24.5%/37.3%, 94.5%/90.4%, 53.0%/60.0%, 86.2%/84.4%, and 47.3%/50.8%, respectively. Accuracy of tumor detection varied widely per anatomic site. Statistically significant interobserver differences were noted, specifically for tumor size of 1-5 cm (P = 0.007) and localization on mesentery and small bowel (kappa = 0.30, P = 0.04). CONCLUSIONS: In colorectal cancer, CT detection of peritoneal carcinomatosis is moderate and of individual peritoneal tumor deposits poor. Interobserver differences are statistically significant. Therefore, preoperative CT seems not to be a reliable tool for detection of presence, size, and location of peritoneal tumor implants in view of treatment planning in patients with colorectal cancer.

Appendiceal Neoplasms↗

Incidence and treatment of recurrent plantar fibromatosis by surgery and postoperative radiotherapy.

BACKGROUND: The incidence of plantar fibromatosis (PF) is unknown. Sometimes PF tends to recur repetitively after surgical treatment. In our institute we have used postoperative radiotherapy in an attempt to diminish the change on recurrence. METHODS: The Dutch Network and National Database for Pathology (PALGA) was consulted to establish the incidence of plantar fibromatosis (PF). Data from 9 patients (11 feet) with PF referred to our institute for recurrent disease were analyzed and the role of postoperative radiotherapy in prevention of recurrence was studied. RESULTS: An average of 1.2 operations for PF was performed per 100,000 citizens yearly in the Netherlands. Twenty-six operations were performed and postoperative radiotherapy was used in 6 cases. Plantar fasciectomy was associated with the lowest recurrence rate. After microscopically incomplete excision or excision of early recurrence (< or =6 months) alone all tumors recurred, while recurrence was rarely observed after adjuvant radiotherapy. However, radiotherapy was associated with significantly impaired functional outcome in 3 cases. CONCLUSIONS: Plantar fibromatosis is relatively rare. Plantar fasciectomy seems to be the operation of choice. Although effective in decreasing the recurrence rate, adjuvant radiotherapy should be used very selectively because of its serious side effects.

Adolescent↗

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↗

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↗

Intraperitoneal chemotherapy for colorectal cancer.

The peritoneal surface remains an important failure site for patients with colorectal cancer. Peritoneal metastases of colorectal cancer are at present considered equal to distant metastatic disease. Consequently, peritoneal carcinomatosis is treated with systemic chemotherapy and surgery only to palliate complications such as obstruction. Despite the development of new chemotherapeutic agents and combinations, the results remain disappointing with a limited impact on survival. Colorectal carcinoma cells are relatively resistant to chemotherapy. Intraperitoneal chemotherapy seems to be an attractive approach in the treatment of high-risk colorectal cancer and peritoneal carcinomatosis from colorectal origin providing high local drug concentration with limited systemic side effects. Adjuvant early postoperative intraperitoneal chemotherapy is worthwhile for consideration as treatment option after resection of high-risk colorectal cancer. In the treatment of peritoneal carcinomatosis postoperative intraperitoneal chemotherapy leads to inadequate exposure of the peritoneal surface. Only an intraoperative intraperitoneal chemotherapy performed with direct cytotoxic drugs such as MMC and cisplatin overcome this problem. The limited drug penetration in tissue implies the need for extensive cytoreductive surgery. The results of phase II studies suggest that an increased median survival can be achieved with this approach. The natural history of this disease and the heterogeneity of the patients are such that only a randomized trial design will adequately answer the question whether regional treatment of patients with peritoneal dissemination of colorectal cancer actually prolongs survival. The results of such a study are to be expected in approximately 2 years time.

Antineoplastic Agents↗

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↗

Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma.

STUDY OBJECTIVES: No established curative treatment is available for pleural thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal malignancies have been treated by cytoreductive surgery and intraoperative hyperthermic intracavitary perfusion chemotherapy (HIPEC). We investigated the feasibility and safety of this multimodality treatment in the thoracic cavity. DESIGN: Patients with pleural thymoma metastases or early-stage MPM were enrolled in a feasibility study. Morbidity, recurrence, and survival rates were recorded. SETTING: The Netherlands Cancer Institute. PATIENTS: Three patients with pleural thymoma metastases and 11 patients with pleural mesothelioma were treated. INTERVENTIONS: Cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy (HITHOC) with cisplatin and adriamycin were performed. The mesothelioma patients received adjuvant radiotherapy on the thoracotomy wound and drainage tracts. MEASUREMENTS AND RESULTS: Morbidity and mortality rates were 47% and 0%, respectively. Reoperation was necessary in four cases. Severe chemotherapy-related complications were not observed. A solitary mediastinal and a contralateral pleural thymoma recurrence were successfully treated by radiotherapy and a contralateral HITHOC procedure. All thymoma patients were alive and free of disease after a mean follow-up period of 18 months. After a mean follow-up period of 7.4 months, nine mesothelioma patients are alive. Two mesothelioma patients died of contralateral pleural and peritoneal recurrent disease, while one patient is alive with locoregional recurrence. CONCLUSIONS: Cytoreductive surgery and HITHOC with cisplatin and adriamycin is feasible in patients with pleural thymoma metastases and early-stage MPM, and is associated with acceptable morbidity rates. Early data on locoregional disease control are encouraging, and a phase II study will be conducted.

Adult↗