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1.
Poult Sci ; 100(2): 1273-1282, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33518084

ABSTRACT

Chicken meat is rich in unsaturated fatty acids. Therefore, it is more susceptible to lipid oxidation and production of volatile organic compounds (VOC). In this study, we evaluated the fatty acids, antioxidants, and VOC profiles of raw and cooked meat samples derived from 4 strains of chicken differing in their growth rates, which were as follows: slow-growing (SG, Leghorn), medium-growing (MG, Hubbard and Naked Neck), and fast-growing (FG, Ross). The VOC profile of meat was measured using proton-transfer reaction-mass spectrometry (PTR-MS). The VOC were identified using PTR-time of flight-MS (PTR-ToF-MS). The data were analyzed using both univariate and multivariate models. Twenty main VOC were identified, which were classified into the following chemical categories: aldehydes, alkadienes, alkenes, furans, amides, alcohols, and other compounds. Our results revealed that the chicken genotype and the method of cooking strongly influenced the VOC profile of the meat. Identifying the relationships between these traits allowed us to highlight the trade-off of the main substrates such as n-3 and n-6 polyunsaturated fatty acids (PUFA), protective substances (antioxidants), and degradation products (VOC) of the poultry meat produced during cooking. The extent of VOC production and n-3 loss was found to be higher for the SG genotype. Reduction of n-6 was higher in MG, whereas small losses in antioxidants and PUFA were observed in the FG genotype, consequently, resulting in the lowest production of VOC. The SG and MG are genotypes more active from a kinetic point of view respect to the FG ones. For this reason, in the FG genotypes, the antioxidants are less involved in the oxidative stress induced by the movement; thus, they were available to protect the lipid of the meat during the cooking process. These results suggested that the use of SG and MG genotypes requires a specific dietary protocol (i.e., increasing the antioxidants content) to counteract the lipid oxidations in all the phases: in vivo, postmortem, and during/after cooking.


Subject(s)
Antioxidants/analysis , Fatty Acids/analysis , Meat/analysis , Volatile Organic Compounds/analysis , Animals , Chickens/classification , Cooking , Lipid Peroxidation , Oxidative Stress , Principal Component Analysis , Thiobarbituric Acid Reactive Substances/analysis , Tocopherols/analysis
3.
Food Chem ; 271: 318-327, 2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30236683

ABSTRACT

Aroma properties of spices are related to the volatile organic compounds (VOCs) present, which can provide distinct analytical signatures. The aim of the study was to examine similarity and diversity of VOC profiles of six common market spices (black/white pepper, chili paprika, cinnamon, nutmeg and saffron). The key volatiles were identified by PTR-TOFMS. Twelve samples per spice were subjected to PTR-Quadrupole MS (PTR-QMS) and Principal Component Analysis to compare the groups and examine diversity. With PTR-TOFMS, 101 volatile compounds were identified as total sum across all samples by mass and comparing them with literature data. Some spices comprised key character aroma compounds, e.g. cinnamaldehyde in cinnamon. For others, VOC groups, such as terpenes, acids and aldehydes topped the list. The PTR-QMS in combination with variables selection resulted in distinct PCA patterns for each spice. Variation within the spice groups was observed, but varied with the kind of spice. The results are valuable for future authentication studies.


Subject(s)
Mass Spectrometry/methods , Spices/analysis , Volatile Organic Compounds/analysis , Protons
5.
Food Chem ; 137(1-4): 142-50, 2013 Apr 15.
Article in English | MEDLINE | ID: mdl-23200002

ABSTRACT

Analytical methods are required in addition to administrative controls to verify the geographical origin of vegetable oils such as palm oil in an objective manner. In this study the application of fatty acid and volatile organic compound fingerprinting in combination with chemometrics have been applied to verify the geographical origin of crude palm oil (continental scale). For this purpose 94 crude palm oil samples were collected from South East Asia (55), South America (11) and Africa (28). Partial least squares discriminant analysis (PLS-DA) was used to develop a hierarchical classification model by combining two consecutive binary PLS-DA models. First, a PLS-DA model was built to distinguish South East Asian from non-South East Asian palm oil samples. Then a second model was developed, only for the non-Asian samples, to discriminate African from South American crude palm oil. Models were externally validated by using them to predict the identity of new authentic samples. The fatty acid fingerprinting model revealed three misclassified samples. The volatile compound fingerprinting models showed an 88%, 100% and 100% accuracy for the South East Asian, African and American class, respectively. The verification of the geographical origin of crude palm oil is feasible by fatty acid and volatile compound fingerprinting. Further research is required to further validate the approach and to increase its spatial specificity to country/province scale.


Subject(s)
Plant Oils/chemistry , Volatile Organic Compounds/analysis , Discriminant Analysis , Fatty Acids/analysis , Geography , Least-Squares Analysis , Palm Oil , Plant Oils/classification
6.
J Agric Food Chem ; 60(33): 8129-33, 2012 Aug 22.
Article in English | MEDLINE | ID: mdl-22844991

ABSTRACT

Organic products tend to retail at a higher price than their conventional counterparts, which makes them susceptible to fraud. In this study we evaluate the application of near-infrared spectroscopy (NIRS) as a rapid, cost-effective method to verify the organic identity of feed for laying hens. For this purpose a total of 36 organic and 60 conventional feed samples from The Netherlands were measured by NIRS. A binary classification model (organic vs conventional feed) was developed using partial least squares discriminant analysis. Models were developed using five different data preprocessing techniques, which were externally validated by a stratified random resampling strategy using 1000 realizations. Spectral regions related to the protein and fat content were among the most important ones for the classification model. The models based on data preprocessed using direct orthogonal signal correction (DOSC), standard normal variate (SNV), and first and second derivatives provided the most successful results in terms of median sensitivity (0.91 in external validation) and median specificity (1.00 for external validation of SNV models and 0.94 for DOSC and first and second derivative models). A previously developed model, which was based on fatty acid fingerprinting of the same set of feed samples, provided a higher sensitivity (1.00). This shows that the NIRS-based approach provides a rapid and low-cost screening tool, whereas the fatty acid fingerprinting model can be used for further confirmation of the organic identity of feed samples for laying hens. These methods provide additional assurance to the administrative controls currently conducted in the organic feed sector.


Subject(s)
Animal Feed/analysis , Food, Organic/analysis , Spectroscopy, Near-Infrared/methods , Discriminant Analysis , Fatty Acids/analysis , Fatty Acids/chemistry , Feasibility Studies , Least-Squares Analysis , Models, Biological , Netherlands
7.
Ned Tijdschr Geneeskd ; 152(9): 501, 2008 Mar 01.
Article in Dutch | MEDLINE | ID: mdl-18389882

ABSTRACT

A 14-year-old male fanatic basketball player with a good skill of dunking presented with skin abnormalities on the right side of his back due to sports-related striae, stretch marks.


Subject(s)
Basketball , Skin Abnormalities/etiology , Skin Abnormalities/pathology , Adolescent , Humans , Male , Skin Abnormalities/diagnosis
8.
J Eur Acad Dermatol Venereol ; 21(5): 678-80, 2007 May.
Article in English | MEDLINE | ID: mdl-17447983

ABSTRACT

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.


Subject(s)
Carcinoma, Squamous Cell/secondary , Leg Ulcer/pathology , Skin Neoplasms/secondary , Vaginal Neoplasms/pathology , Aged, 80 and over , Fatal Outcome , Female , Humans
10.
Ned Tijdschr Geneeskd ; 150(21): 1193-7, 2006 May 27.
Article in Dutch | MEDLINE | ID: mdl-16768285

ABSTRACT

Persistent eosinophilia was diagnosed in a 19-year-old woman with general malaise, dyspnoea attacks, coughing and episodes of angioedema and associated swallowing problems, and in a 21-year-old man with visual problems, dyspnoea, fatigue, reduced appetite, weight loss and gastrointestinal problems. Both had hypereosinophilic syndrome (a rare disease) with organ damage. In both patients, fluorescence-in-situ-hybridisation (FISH) was negative for the fusion gene FIP1L1-PDGFRA (FIPI-like-1-platelet-derived growth factor receptor alpha). The female patient's disease did not respond to either oral corticosteroids or imatinib, but did respond to hydroxycarbamide. The male patient successively received prednisone, interferon alpha and hydroxycarbamide. His eosinophilia progressed nonetheless, but responded partially to imatinib. In addition, the patient underwent an allogenic non-myeloblative stem cell transplantation from his HLA-identical sister. In patients with persistent eosinophilia accompanied by organ damage or organ dysfunction, hypereosinophilic syndrome can be diagnosed providing all secondary causes of the eosinophilia have been ruled out. Complementary investigations should include cytogenetic and clonal analysis to rule out haemopoietic malignancy. Prednisone, hydroxycarbamide, interferon alpha and the promising imatinib are all treatment options.


Subject(s)
Enzyme Inhibitors/therapeutic use , Hypereosinophilic Syndrome , Oncogene Proteins, Fusion/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , mRNA Cleavage and Polyadenylation Factors/genetics , Adult , Benzamides , Diagnosis, Differential , Female , Humans , Hydroxyurea/therapeutic use , Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/genetics , Hypereosinophilic Syndrome/therapy , Imatinib Mesylate , In Situ Hybridization, Fluorescence , Interferon-alpha/therapeutic use , Male , Piperazines/therapeutic use , Prednisone/therapeutic use , Pyrimidines/therapeutic use , Stem Cell Transplantation
11.
Eur J Surg Oncol ; 32(1): 65-71, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16290055

ABSTRACT

AIM: A survival benefit has been observed for colorectal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment modality is associated with a considerable morbidity and mortality and in a significant number of patients survival is not improved. We studied whether poor survivors could be identified on preoperative computed tomography (CT), in order to avoid unnecessary surgery. PATIENTS AND METHODS: Films of abdominopelvic CT scans from 25 such patients treated by cytoreductive surgery and HIPEC were retrospectively analysed by two radiologists separately. A simplified peritoneal cancer index (SPCI) was used to determine the extent of peritoneal involvement. Correlation between the on preoperative CT based SPCI-scores as well as number of involved abdominopelvic areas (N) and survival was examined with the log-rank test. The relation between each affected region and survival was evaluated with Cox regression analysis. RESULTS: The preoperative SPCI- and N-scores of one of the radiologists had no statistically significant prognostic value, while for the second radiologist SPCI > or = 7 and N > or = 4 were associated with particularly poor outcome. Additionally, the presence of ileocaecal region involvement and, depending on the radiologist, the occurrence of tumour deposits in the left subdiaphragmatic area on CT appeared to be unfavourable prognostic signs. CONCLUSIONS: The prognostic value of preoperative conventional CT appeared to be radiologist dependent and may, therefore, be of limited value in selecting colorectal cancer patients with peritoneal carcinomatosis who will not benefit from extensive cytoreductive surgery followed by HIPEC.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma/diagnostic imaging , Colorectal Neoplasms/diagnostic imaging , Hyperthermia, Induced , Laparotomy , Patient Selection , Peritoneal Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Antineoplastic Agents/therapeutic use , Carcinoma/secondary , Carcinoma/therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Follow-Up Studies , Humans , Injections, Intraperitoneal , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Preoperative Care , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
12.
Eur J Surg Oncol ; 31(10): 1145-51, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16084051

ABSTRACT

AIMS: To report the results of standard therapy for peritoneal carcinomatosis of colorectal origin, which consists of conventional surgery and systemic chemotherapy. METHOD: In a prospective study 50 patients with proven peritoneal carcinomatosis of colorectal origin were treated with conventional surgery combined with 5-fluorouracil and leucovorin, or irinotecan in patients treated by 5-fluorouracil within 12 months prior to entry. Survival and progression-free survival were studied and prognostic factors were analysed. RESULTS: The median survival time was 12.6 months. The median time to progression was 7.6 months. Location of primary tumour and result of conventional surgery and systemic chemotherapy were prognostic factors related to survival. CONCLUSION: The survival time of patients with peritoneal carcinomatosis of colorectal origin seems to be increased in patients treated by conventional surgery and systemic chemotherapy when compared to minimal treatment.


Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Adult , Aged , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Peritoneal Neoplasms/secondary , Prognosis , Prospective Studies , Survival Analysis
13.
Br J Surg ; 91(6): 739-46, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15164445

ABSTRACT

BACKGROUND: Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer. Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment option. Patient selection is crucial to outcome. METHODS: Cytoreduction followed by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The following factors were studied for association with survival: perforation and obstruction of the primary lesion, location of the primary lesion, obstruction associated with carcinomatosis, presentation, tumour differentiation and histological type. Extent of disease and completeness of cytoreduction were also studied. Hazard ratios (HRs) were used to study these factors. RESULTS: Location of the primary tumour in rectum (HR 3.14 (95 per cent confidence interval (c.i.) 1.11 to 8.91); P = 0.069), poor differentiation (HR 1.73 (95 per cent c.i. 1.04 to 2.88); P = 0.031) and signet cell histological type (HR 2.24 (95 per cent c.i. 1.21 to 4.16); P = 0.008) were associated with shorter survival. Important factors predicting survival were the number of affected regions (HR 1.38 (95 per cent c.i. 1.20 to 1.59); P < 0.001), the simplified peritoneal cancer score (HR 1.19 (95 per cent c.i. 1.12 to 1.26); P < 0.001) and completeness of cytoreduction (HR 8.54 (95 per cent c.i. 4.01 to 18.18); P < 0.001). No other factor correlated with survival. CONCLUSION: The survival of patients with peritoneal carcinomatosis of colorectal origin is dominated by the extent of disease and the amount of residual tumour after cytoreduction.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/mortality , Colorectal Neoplasms/mortality , Hyperthermia, Induced/methods , Laparotomy/methods , Peritoneal Neoplasms/mortality , Adult , Aged , Carcinoma/therapy , Chemotherapy, Adjuvant , Colorectal Neoplasms/therapy , Combined Modality Therapy/methods , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm, Residual , Peritoneal Neoplasms/therapy , Survival Analysis
14.
Surg Oncol Clin N Am ; 12(3): 771-80, 2003 Jul.
Article in English | MEDLINE | ID: mdl-14567030

ABSTRACT

The favorable pharmacokinetics of MMC, used during intraperitoneal chemotherapy, has been reported in several studies [11-19]. A major safety issue in studies using intraperitoneal chemotherapy perfusion is the resulting systemic drug exposure. The AUCplasma is determined by the dose, the clearance, and the fraction absorbed from the peritoneal cavity. The reported mean plasma peak concentrations are about one-third of the systemic exposure following a therapeutic dose of MMC given by intravenous administration [30]. The best method to quantify the exposure to MMC are the time concentration profiles (AUC). Because MMC can still be found in plasma the day after intraperitoneal administration, the AUC0-90 is an underestimate of the real AUC; extrapolation to infinity gives the most reliable AUCplasma value. In our series the AUCplasma is about half the AUCplasma when given a therapeutic dose MMC intravenously [30]. What is the best dose in intraperitoneal chemotherapy perfusion? The ideal amount of MMC should include a high AUCperfusate, a high AUCplasma and an acceptable systemic toxicity. In our series grade III/IV leucopenia was observed in 28% patients. We find this rather high percentage acceptable as the problem has proved to be transient, and we have experienced no toxic deaths in recent years. In a phase I study it was estimated that a dose of 25 mg/m2 would result in approximately 10% of grade III/IV leucopenia [20]. Our data indicate that dosing based on body surface area is rational and reliable. The variation between individuals is low. Dosing based on a fixed concentration per liter perfusion fluid is probably more liable to have unforeseen variations, given the fact that we deal with linear pharmacokinetics of MMC [20]. As represented in Fig. 3, the dose of MMC can best be administered in three divided doses, resulting in the more equal exposure of peritoneal structures to MMC during the perfusion. It must be emphasized that our findings only hold true for the perfusion system as used in The Netherlands Cancer Institute. This involves a semi-open abdomen, basic perfusate volume of 3 L, perfusion rate of 1 L/min, abdominal temperature of 40 degrees C, 90 minutes of perfusion, and three drug additions (50% at t = 0, 25% at t = 30 and t = 60 minutes). The differences in perfusion techniques make comparisons of published pharmacokinetics data difficult. Cautions comparison suggest that most groups are dosing far below the maximal tolerated dose. We assume that there is a dose-effect relation for MMC. This means that obtaining a maximal safe dose is important to get maximal results. It seems that better dosing of intraperitoneal MMC can still improve results. The pharmacokinetics of intraperitoneal MMC can, however, be influenced by many details. Open or closed perfusion for instance may make some essential differences. It is therefore important that each treatment group performs its own pharmacokinetics studies on intraperitoneal MMC to achieve the optimal dose method for their chemotherapy perfusion setting. In conclusion, the major advantage of intraperitoneal chemotherapy is the regional dose intensity provided. Following intraperitoneal MMC administration, the affected peritoneal surface is exposed to high concentrations while the systemic toxicity is limited. Comparative analyses on MMC pharmacokinetics are difficult to perform because the diversity of treatment techniques. We recommend administration of MMC, divided in three drug additions, based on BSA.


Subject(s)
Carcinoma/drug therapy , Infusions, Parenteral , Mitomycin/pharmacokinetics , Peritoneal Neoplasms/drug therapy , Area Under Curve , Biological Availability , Carcinoma/pathology , Carcinoma/surgery , Chemotherapy, Adjuvant , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Maximum Tolerated Dose , Mitomycin/administration & dosage , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Prognosis , Randomized Controlled Trials as Topic , Treatment Outcome
15.
Eur J Surg Oncol ; 29(8): 682-8, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14511618

ABSTRACT

AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the abundance of mucus in the abdomen without extra-peritoneal growth. METHODS: Our patients with PMP have been treated with cytoreduction and hyperthermic intraperitoneal chemotherapy since 1996. The clinical and histopathological features of PMP and the relation of these features with disease-free interval and survival were assessed. RESULTS: Sixty-two patients with PMP (24 M/38 F) were studied. Adenomatous mucosal changes were present in 31 patients. In females, the ovaries were normal in 5 patients and pseudomyxoma ovarii was present in 20 patients. Patients with minimal atypia and with 1% focal proliferation or less (n=38) had a better survival (p=0.0008) than those with more focal proliferation (n=14). CONCLUSION: In most patients with PMP the appendix is affected; in females the ovaries are usually also involved. Focal proliferation appears to be a prognostic factor.


Subject(s)
Peritoneal Neoplasms , Pseudomyxoma Peritonei , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Disease-Free Survival , Female , Humans , Male , Medical Records , Middle Aged , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/diagnosis , Pseudomyxoma Peritonei/pathology , Pseudomyxoma Peritonei/surgery , Retrospective Studies , Survival Analysis
16.
Anticancer Res ; 23(2B): 1501-8, 2003.
Article in English | MEDLINE | ID: mdl-12820416

ABSTRACT

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C has been applied following cytoreductive surgery for various peritoneal surface malignancies. The aim of this study was to evaluate heat penetration in the abdomen during 10 HIPEC procedures. MATERIALS AND METHODS: Temperature measurements were taken at 5 levels through the abdominal wall. Core temperature and room temperature were also measured. The relationships between the temperature gradient and room or core temperature were studied. RESULTS: At the start of perfusion, the temperature was estimated on average to be 40.6 degrees C at the first level, then it decreased by 1.7 degrees C (SD 1.0 degree C, p = 0.0001) in the first mm. In outward direction, it decreases by a further 1.5 degrees C per cm (SD 0.3 degree C/cm, p < 0.0001). The core temperature influenced the temperature gradient; the room temperature was not found to be a significant factor. At the end of perfusion, the temperature is estimated on average to be 40.1 degrees C at the first level, then it decreased by 0.8 degree C (SD 0.7 degree C, p = 0.011) in the first mm. In an outward direction, it decreased by a further 1.7 degrees C per cm (SD 0.4 degree C/cm, p = 0.0001). No evidence of an association between the temperature gradient and the room temperature or the core temperature was observed. CONCLUSION: Hyperthermia used during HIPEC procedures has a limited penetration depth. The slope in temperature seems to be related to the core temperature.


Subject(s)
Abdominal Wall , Antineoplastic Agents/administration & dosage , Body Temperature , Carcinoma/therapy , Hyperthermia, Induced , Mitomycin/administration & dosage , Peritoneal Neoplasms/therapy , Pseudomyxoma Peritonei/therapy , Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Carcinoma/surgery , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Humans , Infusions, Parenteral , Male , Mitomycin/therapeutic use , Peritoneal Cavity , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/drug therapy , Pseudomyxoma Peritonei/surgery , Temperature
17.
Ann Surg Oncol ; 10(2): 176-82, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12620914

ABSTRACT

BACKGROUND: Malignant pleural mesothelioma (MPM) is a disease mostly confined to the thoracic cavity. Untreated, the median survival is <1 year. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy is used to kill residual tumor cells on the surface of the thoracic cavity while having limited systemic side effects. METHODS: From August 1998 to August 2001, 22 patients with stage I MPM were included in this study. Two patients were irresectable at operation because of extrathoracic tumor growth. Twenty procedures were performed. After cytoreduction, a perfusion was performed with cisplatin and doxorubicin at 40 degrees C to 41 degrees C for 90 minutes. Adjuvant radiotherapy was given to surgical scars and drainage tracts. RESULTS: There was no perioperative mortality, but significant morbidity was seen in 13 patients (65%), including bronchopleural fistula, diaphragm rupture, wound dehiscence, persistent air leakage, and chylous effusion. No hair loss or leucopenia was noticed. The median follow-up was 14 months. The median survival (Kaplan-Meier) was 11 months, with a 1-year survival of 42%. A favorable pharmacokinetic ratio was observed for both cisplatin and doxorubicin. CONCLUSIONS: Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy for stage I MPM is feasible. However, this treatment is accompanied by considerable morbidity. Survival data were less encouraging.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced , Mesothelioma/drug therapy , Mesothelioma/surgery , Pleural Neoplasms/drug therapy , Pleural Neoplasms/surgery , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Doxorubicin/administration & dosage , Female , Humans , Intraoperative Period , Male , Middle Aged , Neoplasm Recurrence, Local , Radiotherapy, Adjuvant , Survival Analysis , Treatment Outcome
18.
Anticancer Drugs ; 14(1): 57-65, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12544259

ABSTRACT

Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) is studied in a phase I study in the treatment of malignant pleural mesothelioma and pleural thymoma. We studied the pharmacokinetics of doxorubicin and cisplatin used during the HITHOC procedure. Furthermore, the penetration characteristics of doxorubicin were examined. Between 1998 and 2001, 24 perfusions were performed with a solution containing doxorubicin and cisplatin for 90 min at 40-41 degrees C. The dose was first based on square meters body surface, whereas in later studies a fixed concentration of the perfusion fluid was used. Samples of blood and perfusion fluid were collected for doxorubicin and cisplatin measurements. The penetration characteristics of doxorubicin in tissue were determined by fluorescence microscopy. The mean AUC(perfusate):AUC(plasma) ratios for doxorubicin and cisplatin (ultrafiltration for plasma) were 99 and 59, respectively. During perfusion the concentration in the perfusate declined essentially according to first-order elimination kinetics for both doxorubicin and cisplatin with half-lives of 74 and 138 min, respectively. At the end of the perfusion, about 35 and 52% of the dose of doxorubicin and cisplatin, respectively, was recovered in the perfusion fluid. One patient developed a nephrotoxicity grade II. No leukopenia or hair loss was seen. Doxorubicin penetrated into the intercostal muscle specimen, albeit that there was considerable variation in distribution throughout the specimen. We conclude that HITHOC with doxorubicin and cisplatin is relatively a safe procedure with the advantage of high intrathoracic cytostatic drug concentrations, while having limited systemic side effects.


Subject(s)
Cisplatin/pharmacokinetics , Doxorubicin/pharmacokinetics , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Thymoma/drug therapy , Adult , Aged , Analysis of Variance , Area Under Curve , Cisplatin/therapeutic use , Doxorubicin/therapeutic use , Female , Humans , Hyperthermia, Induced/methods , Intraoperative Care/methods , Male , Mesothelioma/metabolism , Mesothelioma/surgery , Middle Aged , Pleural Neoplasms/metabolism , Pleural Neoplasms/surgery , Thoracotomy/methods , Thymoma/metabolism , Thymoma/surgery
19.
Ann Surg Oncol ; 9(10): 961-7, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12464587

ABSTRACT

BACKGROUND: Tumor markers are useful for diagnosis and follow-up. We studied the prognostic value of baseline and serial carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) measurements in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Sixty-three patients with pseudomyxoma peritonei were treated with cytoreductive surgery and HIPEC. The tumor markers CEA and CA19.9 were collected before therapy and at 3-month intervals during follow-up. RESULTS: Preoperative CEA and CA19.9 levels were increased in, respectively, 75% and 58% of the patients. Baseline tumor marker values were related to the extent of tumor. Immediately after HIPEC, both tumor markers decreased markedly (P <.0001). CA19.9 was shown to be a more useful tumor marker than CEA for follow-up. During follow-up, a high absolute CA19.9 level (P =.0005) was predictive for imminent recurrence. Patients who never attained a normal CA19.9 level showed a higher recurrence rate at 1 year (53%; SE, 15%), in comparison to patients who did so (6%; SE 4%). The median lead time of increased CA19.9 to recurrence was 9 months. CONCLUSIONS: The measurement of the tumor marker CA19.9 is useful in evaluating therapy in patients with pseudomyxoma peritonei treated with cytoreductive surgery and HIPEC. CA19.9 is a prognostic factor for predicting recurrent disease.


Subject(s)
CA-19-9 Antigen/metabolism , Carcinoembryonic Antigen/metabolism , Peritoneal Neoplasms/diagnosis , Pseudomyxoma Peritonei/diagnosis , Analysis of Variance , Disease-Free Survival , Humans , Netherlands/epidemiology , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/therapy , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Pseudomyxoma Peritonei/mortality , Pseudomyxoma Peritonei/therapy , Recurrence , Survival Rate
20.
Ned Tijdschr Geneeskd ; 146(43): 2036-9, 2002 Oct 26.
Article in Dutch | MEDLINE | ID: mdl-12428464

ABSTRACT

Two female patients, aged 50 and 62 years respectively, who were treated with irinotecan, fluorouracil and folinic acid (Saltz scheme) due to metastasised colorectal carcinoma, developed progressive abdominal pain, fever and leucopenia. One patient also exhibited intestinal obstruction. The main problem was differentiating between an acute abdomen and irinotecan toxicity. Both patients recovered without the need for an operative intervention. One patient was treated by means of colonic stent placement. The combination of gastrointestinal irinotecan toxicity and pre-existing passage problems is dangerous. However, in such cases restraint should be exercised with respect to operative interventions.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/adverse effects , Colorectal Neoplasms/drug therapy , Abdominal Pain/chemically induced , Abdominal Pain/etiology , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/therapeutic use , Female , Fever/chemically induced , Fever/etiology , Humans , Intestinal Obstruction/chemically induced , Intestinal Obstruction/etiology , Irinotecan , Leukopenia/chemically induced , Leukopenia/etiology , Middle Aged , Stents
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