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1.
J Helminthol ; 96: e83, 2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36330684

ABSTRACT

In Serbia, in most cases, small family outbreaks of trichinellosis occur due to the consumption of untested infected meat from domestic pigs that are raised and slaughtered in the backyards of small individual farms. The aim of this study is to present data regarding 24 patients involved in two outbreaks that occurred in two neighbouring districts in Serbia during a closely related period of time in August 2014. The source of infection in the first outbreak was undercooked pork, while raw pork sausages caused the second outbreak. Meat samples and sausages were Trichinella spp. positive by artificial digestion. With the aim to obtain a second opinion and validate the serological findings discovered at the Public Health Institute Nis, all samples were sent to the National Reference Laboratory for Trichinellosis, INEP. Serodiagnosis showed that 21 persons were positive (87.5%) and three (12.5%) were negative for anti-Trichinella antibodies, while 15 patients fulfilled the trichinellosis case definition. Western blot analysis (using an epitope unique for the muscle larvae stage of the Trichinella genus) confirmed the diagnosis of trichinellosis in five patients. Six patients also had specific antibodies against Toxocara canis (T. canis). Due to the fact that in endemic foci in Serbia there is the presence of Trichinella spiralis and T. canis and that these two infections could be asymptomatic, we consider that trichinellosis cases were irrefutably proven. The dilemma about the existence of co-infection with T. canis remained open due to the lack of clinical findings.


Subject(s)
Coinfection , Toxocara canis , Trichinella , Trichinellosis , Swine , Animals , Trichinellosis/diagnosis , Trichinellosis/epidemiology , Trichinellosis/veterinary , Toxocara , Coinfection/epidemiology , Serbia/epidemiology , Disease Outbreaks , Meat , Sus scrofa
2.
J Helminthol ; 96: e71, 2022 Oct 03.
Article in English | MEDLINE | ID: mdl-36189624

ABSTRACT

Trichinellosis is an important worldwide foodborne zoonosis. The gold standard test to detect Trichinella spp. larvae in muscle samples of animals intended for human consumption is the artificial digestion method. Handling and dispensing of conventional pepsin powder present significant safety risks for analysts. The use of pepsin powder that is resistant to aerosolization should alleviate these safety concerns. The aim of this study was to compare the efficacy of an aerosol-resistant pepsin powder to conventional pepsin powder in the artificial digestion method. Proficiency samples of pork diaphragm containing specific numbers of viable Trichinella spiralis larvae were tested in two laboratories. The results revealed that aerosol-resistant pepsin was simple, effective and convenient to use, and showed good solubility and larval recovery that met the requirements of the European Union regulation EU 2015/1375. Overall, the efficacy of the aerosol-resistant pepsin was comparable to the conventional pepsin and safer for analysts.


Subject(s)
Trichinella spiralis , Trichinella , Trichinellosis , Aerosols , Animals , Digestion , Food Inspection/methods , Food Parasitology , Humans , Larva , Meat , Pepsin A , Powders , Trichinellosis/diagnosis , Trichinellosis/prevention & control , Trichinellosis/veterinary
3.
J Helminthol ; 96: e35, 2022 May 24.
Article in English | MEDLINE | ID: mdl-35606907

ABSTRACT

Trichinellosis in humans is most often caused by the parasite Trichinella spiralis. The clinical course of the disease is diverse and the symptoms can vary from mild to severe. Symptoms usually disappear within a few months, but encysted larvae in the muscles can cause myalgia and weakness that last for years. However, the existence of chronic trichinellosis as a disease is still debatable. This study presents the results obtained at the National Reference Laboratory for Trichinellosis - INEP, Serbia. The study was conducted to assess the immunoserological, biochemical and symptomatic disease parameters of twelve patients who acquired trichinellosis 13 and 18 years ago, respectively. They were involved in two T. spiralis outbreaks in Serbia, at the village of Kumane and the city of Belgrade (nine and three patients, respectively). Results indicated the presence of specific anti-Trichinella antibodies in 83% of the total number of patients. However, while the humoral immune response to Trichinella lasted for more than a decade reaching almost two decades after the acute infection phase (7/9 and 3/3 respectively, in two outbreaks), persistence of chronic muscular pain, as the most prolonged symptom of trichinellosis, could be found in the majority of patients from the Kumane outbreak (7/9). As a consequence, these patients suffered from limitations in daily living activities for the same period of time. The results presented in this paper are our contribution to the view that trichinellosis as a chronic disease with symptoms exists and may be related to the severity of the disease in the acute phase.


Subject(s)
Trichinella spiralis , Trichinella , Trichinellosis , Animals , Disease Outbreaks , Humans , Muscles/parasitology , Trichinellosis/parasitology
4.
Med Mal Infect ; 50(6): 520-524, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31732242

ABSTRACT

OBJECTIVES: We aimed to describe the first cases of human trichinellosis due to Trichinella britovi in Serbia. A large trichinellosis outbreak due to the consumption of wild boar meat products took place during the 2015-2016 winter. PATIENTS AND METHODS: In January 2016, the Department of Infectious Diseases in Uzice examined 111 individuals with clinical and biological signs of trichinellosis, of whom 19 were hospitalized. Trichinella species identification was performed by multiplex PCR. Serodiagnosis was performed using immunofluorescence antibody assay, indirect ELISA, and Western Blot as confirmatory tests. RESULTS: The main symptoms included myalgia (83%), weakness (82%), joint pain (80%), fever (77%), facial edema (74%), and diarrhea (23%). Eosinophil levels>500/µl were observed in 98% of patients. Elevated CPK levels were detected in 71% of patients and elevated LDH levels in 75%. Three patients had cardiac complications. Treatment included mebendazole, nonsteroidal anti-inflammatory drugs, and corticosteroids. Anti-Trichinella antibodies were observed in 89.7% of patients two months after disease onset, including all hospital-treated patients. Among them, serum positivity detected one year later was 100%. CONCLUSIONS: This outbreak highlighted communication failures, from hunters to consumers. Awareness should be raised on the relation between trichinellosis and game meat. Trichinella species detection is important for adequate outbreak recording and could contribute to better understanding the clinical and serological signs of T. britovi infection.


Subject(s)
Disease Outbreaks , Food Parasitology , Meat Products/parasitology , Trichinellosis/diagnosis , Trichinellosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Serbia/epidemiology , Young Adult
5.
J Helminthol ; 93(1): 33-41, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29168448

ABSTRACT

Infection with parasites from the Trichinella genus occurs in many vertebrates but disease only occurs in humans (trichinellosis). Humans are infected after the consumption of raw or undercooked meat from infected wild or domestic animals (usually swine or horses). Using the monoclonal antibody (mAb) 7C2C5, specific for an epitope unique to the muscle larvae of the genus Trichinella, we have developed a competitive enzyme-linked immunosorbent assay (c-ELISA) that enables the rapid detection of Trichinella-specific antibodies in sera originating from two different host species (human, swine) infected with either Trichinella spiralis or Trichinella britovi. This novel c-ELISA exhibited 100% specificity and sensitivity, as confirmed by a Western blot test. The assay is easy to use (one incubation step), and the time required for the procedure (45 min) is shorter than in any other ELISA format. This test could be useful for both the detection and surveillance of Trichinella infections.


Subject(s)
Enzyme-Linked Immunosorbent Assay/standards , Parasitology/methods , Swine/parasitology , Trichinella/isolation & purification , Trichinellosis/diagnosis , Trichinellosis/veterinary , Animals , Antibodies, Helminth/blood , Antibodies, Monoclonal/immunology , Antigens, Helminth/immunology , Antigens, Helminth/isolation & purification , Horses/parasitology , Humans , Larva/immunology , Meat/parasitology , Reproducibility of Results , Sensitivity and Specificity , Time Factors , Trichinella/immunology , Trichinella spiralis/immunology , Trichinella spiralis/isolation & purification , Trichinellosis/blood
6.
Comp Immunol Microbiol Infect Dis ; 34(5): 429-39, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21903269

ABSTRACT

Parasitic nematode Trichinella spiralis exert immunomodulatory effect on the host immune response through excretory-secretory products (ES L1) released from the encysted muscle larvae. Rat bone-marrow derived dendritic cells (DCs) stimulated with ES L1 antigens acquire semi-matured status and induce Th2 and regulatory responses in vitro and in vivo. Priming naïve T cells in vitro with ES L1 pulsed DCs caused strong Th2 polarization, accompanied by elevated production of regulatory cytokines IL-10 and TGF-ß and no increase in the proportion of CD4+CD25+Foxp3+ among the effector T cell population. In vivo T cell priming resulted in mixed Th1/Th2 cytokine response, with the dominance of the Th2 type and elevated levels of regulatory cytokines. Significant increase in the proportion of CD4+CD25+Foxp3+ cells was found among recipient's spleen cells. We have achieved to create immune status characteristic for the live infection by in vivo application of DCs educated with ES L1 antigens.


Subject(s)
Antigens, Helminth/immunology , Dendritic Cells/immunology , Helminth Proteins/immunology , Larva/immunology , Trichinella spiralis/immunology , Animals , Bone Marrow Cells/immunology , CD4 Lymphocyte Count , Coculture Techniques , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunity, Cellular , Interleukin-10/immunology , Larva/chemistry , Larva/pathogenicity , Lymphocyte Activation , Rats , Rats, Wistar , T-Lymphocytes/immunology , Transforming Growth Factor beta/immunology , Trichinella spiralis/chemistry , Trichinella spiralis/pathogenicity , Trichinellosis/immunology , Trichinellosis/parasitology
7.
Vet Parasitol ; 159(3-4): 229-31, 2009 Feb 23.
Article in English | MEDLINE | ID: mdl-19041181

ABSTRACT

The influence of host genetics on the susceptibility to primary Trichinella spiralis infection has been extensively studied in a mouse model, but has not been clarified for rats. Analyses of interstrain and intrastrain genetic variation in response to infectious agents could be beneficial not only for elucidating the genetic basis of host resistance/susceptibility, but for revealing immune response mechanisms as well. The aim of this study was to analyse interstrain differences in worm burdens and cytokine production between Albino Oxford (AO) and Dark Agouti (DA) rats in muscle phase of T. spiralis infection. Clear strain-dependent variation was observed in the number of T. spiralis larvae per gram (lpg) of muscle tissue where values for DA rats (626.7+/-171lpg) vastly exceeded those found in AO rats (49.8+/-25.9lpg, p<0.001). Differences between the strains were also noticed in key cytokine levels. In infected AO rats, the cytokine production remained in favor of Th1 type response, while infected DA rats showed a shift towards a Th2 type response. The level of regulatory IL-10 was significantly increased only in T. spiralis infected DA rats. Our results provide evidence that DA rats express higher susceptibility to T. spiralis infection in comparison to AO rats with respect to muscle larvae burden. The infection in DA rats was accompanied by the production of anti-inflammatory cytokines, while the response of AO rats was characterized by a proinflammatory type of immune response.


Subject(s)
Genetic Predisposition to Disease , Trichinella spiralis/physiology , Trichinellosis/genetics , Animals , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation/physiology , Larva , Muscle, Skeletal/metabolism , Muscle, Skeletal/parasitology , Rats
8.
Parasite Immunol ; 30(9): 491-5, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18627506

ABSTRACT

Pathogen-derived products have the capacity to induce maturation of bone marrow-derived dendritic cells (BMDCs)into populations of effectors cells that polarize Th cells toward Th1 or Th2 phenotype via different mechanisms. Since those mechanisms are not entirely clear for helminths, and almost completely unknown for Trichinella spiralis(TS), we started an investigation of the effects of TS antigens (four different antigens isolated from all three life-cycle stages of parasite)on maturation of BMDCs and their potential to present TS antigens. The expression of MHC class II, costimulatory molecules CD86, CD54, IL-10 and IL-12p70 cytokine production were measured after 2 days of BMDCs cultivation with TS antigens. While parasitic antigens did not significantly alter the expression of MHC II, most of them, except crude muscle larvae antigens, up-regulated the expression of costimulatory molecules. BMDCs, primed with all TS antigens, released increased amounts of IL-10 and decreased amounts of IL-12p70. BMDCs, primed with TS antigens, induced significant proliferation of syngeneic TS sensitized lymph nodes cells and also stimulated the production of IL-4 by T cells purified from of TS infected DA rats. The results indicate that TS stimulated BMDCs leads to the polarization of the immune response towards regulatory and Th2 type.


Subject(s)
Antigens, Helminth/immunology , Dendritic Cells/immunology , Trichinella spiralis/immunology , Trichinellosis/immunology , Animals , Rats , Rats, Wistar , T-Lymphocytes, Regulatory/immunology , Th2 Cells/immunology
9.
Int J Gynecol Cancer ; 17(2): 373-8, 2007.
Article in English | MEDLINE | ID: mdl-17362315

ABSTRACT

The purpose of this study was to estimate the response rate of 26-h continuous infusion cyclosporine A (CSA) combined with carboplatin (CBDCA) and subcutaneous alpha-interferon (IFN), in recurrent ovarian cancer (OC), and to measure their effects on CBDCA pharmacokinetics. OC patients relapsing following platinum-based chemotherapy received CBDCA area under the curve (AUC 3) with CSA and IFN, every 3 weeks. The pharmacokinetics of CSA and CBDCA were determined in a subset of patients. Thirty patients received 84 courses of therapy. Three partial responses were observed. Nine patients were stable for >4 months. Toxicity was similar to that observed in our previously reported phase I study and consisted of myelosuppression, nausea, vomiting, and headache. The mean end of infusion CSA level (high-performance liquid chromatographic assay [HPLC]) was 1109 +/- 291 microg/mL (mean +/- SD). CBDCA pharmacokinetics revealed a measured AUC of 3.61 versus a targeted AUC of 3, suggesting a possible effect of IFN on CBDCA levels versus errors in the estimation of CBDCA clearance using measured creatinine clearance. Steady-state levels of >1 microg/mL CSA (HPLC assay) are achievable in vivo. Insufficient clinical resistance reversal was observed in this study to warrant further investigation of this combination.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , California , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carboplatin/pharmacokinetics , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Cyclosporine/pharmacokinetics , Drug Resistance, Neoplasm/drug effects , Female , Humans , Infusions, Intravenous , Injections, Subcutaneous , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Interferon-alpha/pharmacokinetics , Middle Aged , Treatment Outcome
10.
Int J Gynecol Cancer ; 16(2): 814-20, 2006.
Article in English | MEDLINE | ID: mdl-16681767

ABSTRACT

The purpose of the study was to evaluate tamoxifen-associated changes in the vagina and uterus in postmenopausal breast cancer patients. Between June 1994 and December 1998, 45 patients enrolled in a prospective study before commencing tamoxifen therapy. Patients with endometrial thickness >5 mm or neoplasia were excluded. Transvaginal ultrasonography, vaginal maturation indexes (VMI), and endometrial biopsy were performed at baseline and repeated at 6 months (n= 42), 1 year (n= 39), 2 years (n= 32), 3 years (n= 26), 4 years (n= 19), and 5 years (n= 15). For the 39 patients followed for 1 year, VMI (% parabasal/intermediate/superficial) was 21/71/8 at baseline compared with 1/90/9 at 1 year (P value = 0.0008/0.001/0.78). At baseline, mean endometrial thickness and uterine volume were 2.6 mm and 64 cm(3), respectively, compared with 5.8 mm and 84 cm(3) at 1 year (P= 0.0002, 0.002). At baseline, 80% of patients had atrophic endometrium and 9% proliferative endometrium compared with 61% and 26% at 1 year, respectively (P= 0.04). No cases of endometrial hyperplasia or adenocarcinoma were detected. Findings observed at 6 months persisted through 5 years of follow-up. Tamoxifen exerts a weak estrogenic effect on the vagina and uterus in highly prescreened postmenopausal women without preexisting endometrial pathology.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Postmenopause , Tamoxifen/therapeutic use , Uterus/drug effects , Adult , Aged , Aged, 80 and over , Endometrium/drug effects , Female , Humans , Middle Aged , Postmenopause/drug effects , Postmenopause/physiology , Prospective Studies
11.
Khirurgiia (Sofiia) ; 58(1): 8-10, 2002.
Article in Bulgarian | MEDLINE | ID: mdl-12515026

ABSTRACT

Liver resection in a patient with cirrhosis carries increased risk. The purposes of this study were to review the results of cirrhotic liver resection in the past decade and to propose strategies for low morbidity and mortality. From January 1991 to December 2000 73 patients with primary liver cancer (PLC) were operated and identified in a retrospective database. Twenty five (34%) patients had underlying cirrhosis: 14--Child A and 11--Child B. There were 18 male and 7 female with mean age 60.9 +/- 9.2 (from 44 to 78). There were 16 (64%) resections: 11--stage Child A and 5--stage Child B. Major resections were 7 and minor--9. Eight patients received hemotransfusion--mean 939.13 ml (370-2000 ml). Four patients (25%) died of the hepatic resection--by the 30-th day. Seven patients had postoperative complications. 4 patients developed liver failure. Major resections had 42.86% mortality, minor resections--11.11%. Hepatic resection is potentially curative therapy for HCC and cirrhosis especially in Child A. Child B produce high rate of postoperative morbidity and mortality.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Cirrhosis/surgery , Liver Neoplasms/surgery , Postoperative Complications/mortality , Adult , Aged , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/mortality , Female , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Neoplasms/complications , Liver Neoplasms/mortality , Male , Middle Aged , Retrospective Studies
12.
J Surg Oncol ; 78(3): 194-200; discussion 200-1, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11745806

ABSTRACT

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.


Subject(s)
Brain Neoplasms/secondary , Ovarian Neoplasms/pathology , Aged , Brain Neoplasms/mortality , Brain Neoplasms/therapy , Combined Modality Therapy , Female , Humans , Meta-Analysis as Topic , Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Prognosis , Survival Rate
13.
J Am Coll Surg ; 193(6): 626-32, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11768679

ABSTRACT

BACKGROUND: The purpose of this study was to determine the morbidity and survival associated with bowel resection at the time of primary cytoreductive surgery for ovarian cancer. STUDY DESIGN: We reviewed all patients undergoing bowel resection by gynecologic oncology faculty at the time of primary cytoreduction for advanced epithelial ovarian cancer diagnosed between 1983 and 1995. RESULTS: There were 105 patients meeting the above criteria. The median age was 65 years (range 34 to 85 years). There were 76 stage III and 25 stage IV cancers. The primary indication for bowel resection was tumor debulking in 92% of the patients. Seventy patients had segmental resection of the colon only, and 22 patients underwent resections that included the large and small bowels. Mean operating time was 260 minutes and mean estimated blood loss was 1,447 mL. Thirty-three (31%) patients were optimally cytoreduced to less than 1 cm residual disease. Ten patients experienced major complications directly related to bowel resection, including bowel fistula (4 patients), early postoperative bowel obstruction (5 patients), and stomal hernia (1 patient). Other morbidity included ileus for more than 10 days (18 patients), cardiac complications (17 patients), pneumonia (8 patients), sepsis (5 patients), and thromboembolism (4 patients). Six patients died and five patients required reexploration within 30 days of operation. Patients with preoperative bowel obstruction and suboptimal residual disease were more likely to have postoperative morbidity. Median survival in the optimally debulked patients was 35 months compared with 18 months in patients suboptimally cytoreduced (p = 0.006). Multivariate analysis demonstrated that optimal debulking (p = 0.009) and platinum chemotherapy (p = 0.00006) were independently associated with improved survival. Age, International Federation of Gynecologia Oncologists stage, American Society of Anesthesiologists class, and paclitaxel chemotherapy did not influence survival. CONCLUSIONS: In patients undergoing bowel resection at the time of primary cytoreduction for ovarian cancer, optimal cytoreduction to less than 1 cm residual disease results in improved survival. Morbidity is common but is comparable to other published series of ovarian cancer patients undergoing primary cytoreductive surgery without bowel resection. Additionally, patients with preoperative bowel obstruction and suboptimal residual disease are more likely to have serious morbidity.


Subject(s)
Intestines/surgery , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Digestive System Surgical Procedures , Female , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intraoperative Complications , Life Tables , Middle Aged , Ovarian Neoplasms/complications , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Postoperative Complications , Retrospective Studies , Survival Analysis
14.
Bone Marrow Transplant ; 28(9): 859-63, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11781646

ABSTRACT

This study was performed in order to evaluate the toxicities, progression-free and overall survival of patients with responsive residual or recurrent ovarian cancer treated with high-dose chemotherapy. Twenty-seven patients were treated. Doxorubicin, 165 mg/m(2) over 96 h (days -12 to -8), etoposide 700 mg/m(2) every day x3 (days -6 to -4), and cyclophosphamide 4.2 g/m(2) on d -3 was followed by stem cells and granulocyte colony-stimulating factor. The median days of granulocyte count <500/microl was 14 (range 10-42) and platelets <20,000/microl was 13 (range 2-80). Median numbers of red cell and platelet transfusions were 15 (5-16) and 14 (4-103). Toxicity included mucositis requiring narcotic analgesia in all patients. Asymptomatic decreases in ejection fraction to values <50% were observed in four patients. No clinical congestive heart failure was observed. One death due to sepsis was observed. Median progression-free survival is 7.5 months (1.0-56 months); five patients remain alive, two of whom remain progression-free at 19.5 and 24.5 months post transplant. Median overall survival is 14.0 months (1-68 months). We conclude that high-dose anthracyclines may be safely administered to ovarian cancer patients. The short overall and progression-free survivals observed in our population suggest that this combination is not optimal.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Hematopoietic Stem Cell Transplantation , Ovarian Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/analysis , CA-125 Antigen/analysis , Carcinoma/blood , Carcinoma/mortality , Carcinoma/surgery , Carcinoma/therapy , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Neoplasm Proteins/analysis , Ovarian Neoplasms/blood , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Ovarian Neoplasms/therapy , Ovariectomy , Survival Analysis , Transplantation, Autologous , Treatment Failure , Treatment Outcome
15.
Gynecol Oncol ; 73(3): 402-6, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10366467

ABSTRACT

OBJECTIVE: The purpose of this study was to examine ovarian histopathology in tamoxifen-treated breast cancer patients undergoing oophorectomy. METHODS: We reviewed the records and ovarian histopathology of 152 breast cancer patients who underwent oophorectomy at a single institution between January 1980 and October 1996. At the time of oophorectomy, 99 patients had never received tamoxifen, 44 patients were currently receiving tamoxifen, and 9 patients had previously received tamoxifen. Patient demographic and medical data and indication for oophorectomy were examined. Ovarian histopathology was classified as normal, functional ovarian cyst, benign ovarian tumor, endometriosis, ovarian cancer, and metastatic cancer. RESULTS: Patient characteristics and indication for oophorectomy did not differ significantly based on tamoxifen exposure. There was no difference in the occurrence of benign ovarian tumors, functional ovarian cysts, or metastatic breast cancer based on tamoxifen exposure. Tamoxifen-treated patients were less likely to have ovarian cancer, 0 of 53 patients (95% confidence interval (CI): 0.0%, 6.7%) compared with 10 of 99 patients (95% CI: 5.0%, 17.8%) patients not receiving tamoxifen (P = 0.015). Endometriosis was slightly more common in patients currently receiving tamoxifen, but the difference was not statistically significant. CONCLUSIONS: In women undergoing oophorectomy, there was no evidence that tamoxifen exposure was associated with an increase in benign or malignant primary or metastatic ovarian neoplasm or in functional ovarian cysts. Further study is necessary to better define any association between tamoxifen and endometriosis and the effect of tamoxifen on ovarian cancer risk.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Ovary/drug effects , Ovary/pathology , Tamoxifen/therapeutic use , Adult , Aged , Female , Humans , Middle Aged
16.
Gynecol Oncol ; 69(3): 243-7, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9648595

ABSTRACT

Cervical carcinoma frequently metastasizes to the paraaortic region, necessitating extended field radiotherapy to effect a cure. As imaging modalities are unreliable in identifying all cases of paraaortic nodal metastases (PAN), surgical staging is often utilized prior to radiotherapy. This study was aimed at identifying factors predictive of survival in women with cervical carcinoma and paraaortic metastases. In particular, survival based on extent of paraaortic disease was examined. The study group consisted of 43 women (stages IB-IVB) identified between 1982 and 1993 who were treated with extended field radiation for cervical carcinoma with histologically confirmed paraaortic metastases. The estimated 5-year survival for the study population was 24% with a median survival of 18 months. Pelvic tumor size had a significant impact on survival with the median survival being 34 months if the primary lesion was < 6 cm compared to 14 months if > or = 6 cm (P = 0.01). Eight of the 26 (31%) women without residual PAN disease after surgical staging remain alive and disease free (mean follow-up, 74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is alive 71 months after treatment (P = 0.05). However, a comparison of Kaplan-Meier survival curves did not show a statistically significant advantage to the surgical excision of grossly involved PAN (P = 0.98). Although long-term survival among women with grossly involved, unresected paraaortic metastases is uncommon, further study is necessary to elucidate the role of surgical excision of bulky aortic disease in women with cervical cancer.


Subject(s)
Carcinoma, Squamous Cell/secondary , Lymph Node Excision , Lymph Nodes/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Aorta , Carcinoma, Adenosquamous/secondary , Carcinoma, Adenosquamous/surgery , Carcinoma, Squamous Cell/surgery , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Analysis , Uterine Cervical Neoplasms/surgery
17.
Cancer Res ; 58(13): 2793-800, 1998 Jul 01.
Article in English | MEDLINE | ID: mdl-9661893

ABSTRACT

In this Phase I study, the maximally tolerated doses (MTDs) of i.p. iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin (LV) were determined. The pharmacokinetics and pharmacological advantage of IdUrd were evaluated, and flow cytometric analysis allowed examination of the extent of incorporation of IdUrd into tumor cells with and without the addition of i.v. LV. Thirty-nine patients with advanced neoplasms primarily confined to the peritoneal space were enrolled in a dose-escalation trial using 4-h dwells of IdUrd administered i.p. daily for 4 days with and without an i.v. infusion of LV 500 mg/m2/day for 4.5 days. Twenty-three patients received single-agent therapy, and 13 patients received i.p. IdUrd in combination with i.v. LV. The MTD of single-agent IdUrd administered on this schedule was 4125 mg/m2/day for 4 days; and that of the IdUrd in combination was 3438 mg/m2/day. Dose-limiting toxicities were myelosuppression and stomatitis. During the period of the dwell, the peritoneal AUC (area under the curve) of IdUrd exceeded the plasma AUC of IdUrd by one or two orders of magnitude in all patients at all doses tested; there was a possible effect of LV on peritoneal AUC. The geometric mean pharmacological advantage (AUCperitoneal/ AUCplasma) was 181 at 625 mg/m2/day and 90 at 4538 mg/m2/day. Flow cytometric analysis suggests saturation of IdUrd measured in DNA at the 2500-3125 mg/m2 dose level, without an increase after the addition of LV. Twelve patients received 4-12 courses of therapy. One patient with recurrent ovarian cancer who received 16 courses of therapy experienced complete resolution of her ascites, near normalization of CA-125 levels, and improved quality of life; two patients with high-risk tumors receiving "adjuvant" therapy are disease-free at 3 and 6 years after treatment; other patients experienced transient clearing of ascites. The recommended Phase II dose of i.p. IdUrd using a 4-h dwell daily for 4 days is 3750 mg/m2/day alone or 3125 mg/m2/day in combination with continuous i.v. LV at 500 mg/m2/day for 4.5 days. Although flow cytometric data suggest that DNA incorporation of IdUrd is not affected by the addition of LV, the cytotoxicity of the combination regimen may be increased due to LV-enhanced, IdUrd-related inhibition of thymidylate synthase. For this reason, we recommend that efficacy studies of the combination continue in parallel with studies of IdUrd alone.


Subject(s)
Antidotes/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Idoxuridine/administration & dosage , Leucovorin/administration & dosage , Peritoneal Neoplasms/drug therapy , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/pharmacokinetics , CA-125 Antigen/blood , DNA, Neoplasm/metabolism , Drug Administration Schedule , Drug Therapy, Combination , Female , Gastrointestinal Neoplasms/blood , Gastrointestinal Neoplasms/drug therapy , Humans , Idoxuridine/adverse effects , Idoxuridine/pharmacokinetics , Injections, Intraperitoneal , Injections, Intravenous , Male , Middle Aged , Ovarian Neoplasms/blood , Ovarian Neoplasms/drug therapy , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/drug therapy , Peritoneal Neoplasms/blood
18.
Am J Obstet Gynecol ; 178(6): 1145-50, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9662294

ABSTRACT

OBJECTIVE: This study was conducted to examine the histopathologic changes in tamoxifen-treated postmenopausal patients with endometrial thickness > or = 5 mm with transvaginal ultrasonography. STUDY DESIGN: Thirty-five tamoxifen-treated postmenopausal breast cancer patients underwent transvaginal pelvic ultrasonography with endometrial thickness > or = 5 mm followed by either curettage-hysteroscopy (n = 24), or hysterectomy (n = 11). Endometrial histopathologic findings were examined. RESULTS: Overall, endometrial polyps were the most common histopathologic finding (23 of 35 patients). Endometrial cystic atrophy was uncommonly detected in patients undergoing curettage-hysteroscopy (1 of 24 patients) compared with patients undergoing hysterectomy (9 of 11 patients). No cases of endometrial cancer or hyperplasia were detected. CONCLUSIONS: Endometrial polyps were a frequent finding in tamoxifen-treated postmenopausal women who had endometrial thickness > or = 5 mm with the use of transvaginal ultrasonography. Endometrial cystic atrophy may explain "thickened endometrium" on transvaginal ultrasonography in this patient population with no evidence of endometrial polyps, hyperplasia, or adenocarcinoma after surgical evaluation.


Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/drug therapy , Cysts/diagnostic imaging , Endometrium/diagnostic imaging , Postmenopause/physiology , Tamoxifen/adverse effects , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Atrophy , Curettage , Endometrium/drug effects , Endometrium/pathology , Female , Humans , Hysterectomy , Middle Aged , Polyps/chemically induced , Polyps/diagnostic imaging , Polyps/pathology , Retrospective Studies , Tamoxifen/therapeutic use , Ultrasonography , Uterine Diseases/chemically induced , Uterine Diseases/diagnostic imaging , Uterine Diseases/pathology
20.
Am J Clin Oncol ; 19(5): 433-8, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8823468

ABSTRACT

Sixty-one patients with FIGO IB cervical cancer treated with planned preoperative radiotherapy (dose to point A: 52-93 Gy, mean 73 Gy) and hysterectomy from 1969 to 1993 were retrospectively reviewed. Patient characteristics and treatment parameters and their association with residual tumor in the hysterectomy specimen were analyzed. Glandular (adenocarcinoma and adenosquamous) tumors were smaller than squamous tumors: 6/11 (55%) were < 6 cm in diameter, versus 12/50 (24%) squamous tumors (p = 0.03). Glandular tumors had a higher incidence of residual disease: 10/11 (91%) versus 24/50 (48%) (p = 0.01). There was no association between presence of pathologic residual disease in the hysterectomy specimen and tumor size, morphology (endophytic vs. exophytic), patient age, dose to point A, time to deliver radiotherapy, or interval between radiotherapy and hysterectomy. Overall 34/61 (56%) patients had residual disease in their hysterectomy specimens after planned preoperative radiotherapy. There were significantly more glandular tumors than squamous tumors with residual disease, even though glandular tumors were a group of smaller tumors.


Subject(s)
Hysterectomy , Uterine Cervical Neoplasms/therapy , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Adult , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/radiotherapy , Carcinoma, Adenosquamous/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Female , Humans , Neoplasm, Residual , Radiotherapy Dosage , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery
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