ABSTRACT
One of the main reasons of failure of dacryocystorhinostomy (DCR) is cicatricial closure of the ostium. Finding a way to prevent this outcome remains one of the leading aims of research in dacryology. The effectiveness of the most widespread methods is often considered contradictory by various researchers. Pirfenidone is a small-molecule agent that demonstrated good antifibrotic effect and low toxicity in previous in vitro research. There haven't been any in vivo studies of its intraoperative use in DCR.Purpose - to determine the in vivo efficacy of pirfenidone in prevention of ostium cicatricial closure following dacryocystorhinostomy in an animal experiment. MATERIAL AND METHODS: The study was conducted on 18 Chinchilla rabbits. They were divided into 3 groups and each animal underwent modified dacryocystorhinostomy. On the final stage of surgery rabbits of group 1 were injected 1 ml of 0.15 mg/ml pirfenidone solution, rabbits of group 2 - 0.3 mg/ml pirfenidone solution. No injections were performed in group 3. Animals were terminated on days 7 (6 rabbits), 14 (6 rabbits) and 28 (6 rabbits) following surgery. Lacrimal stoma patency was evaluated in vivo by irrigation, and morphologically postmortem. Tissue samples obtained from the stoma area were examined histologically for signs of fibrosis. RESULTS: Failure of dacryocystorhinostomy was observed in 4 out of 18 cases: all rabbits of group 3 terminated on days 14 and 28. The most pronounced morphological signs of fibrosis were also noted in group 3. No topical or systemic adverse effects of the medication were observed in groups 1 and 2. CONCLUSION: Pirfenidone demonstrated high antifibrotic efficacy and low toxicity in experimental dacrycystorhinostomy in rabbits. These results provide grounds for further research into the use of pirfenidone in dacrycystorhinostomy.
Subject(s)
Cicatrix/prevention & control , Dacryocystorhinostomy , Nasolacrimal Duct , Pyridones/therapeutic use , Animals , Dacryocystorhinostomy/adverse effects , Endoscopy , Nasolacrimal Duct/surgery , Rabbits , Treatment OutcomeABSTRACT
INTRODUCTION: Fibrosis is the most important pathologic condition involved in undesirable outcomes of dacryocystorhinostomy. A number of biochemical factors are currently known to have an effect on wound healing by promoting excessive scarring. Isoforms of transforming growth factor ß (TGF-ß1) are considered the 'main' pro-fibrotic factor, but wound healing is also affected by other cytokines such as connective tissue growth factor (CTGF), which stimulates fibrosis, and fibroblast growth factor (FGF-2), which acts as antagonist to it. PURPOSE: To investigate correlations between endoscopic endonasal dacryocystorhinostomy outcomes and certain mediators of fibrosis. MATERIAL AND METHODS: The study included 45 cases of endoscopic endonasal dacryocystorhinostomy. The patients were grouped according to surgery outcome: patients with unsuccessful surgical treatment were assigned to group 1 (n=10); patients with successful surgical treatment - to group 2 (n=34). One patient was excluded from the study. Full-layer biopsy specimen were taken from patients' nasal mucosa before the surgery. TGF-ß1, TGF-ß2, TGF-ß3, CTGF, FGF-2 concentrations were evaluated using ELISA and normalized by total protein concentration. RESULTS: Surgical failure was observed in 10 cases (22.72%). CTGF concentration was significantly correlated with negative outcome (p<0.05) and was elevated in most specimen obtained from group 1. No significant correlation was noted between the concentrations of other evaluated cytokines in nasal mucosa specimens and the surgical outcome. CONCLUSION: The study found a correlation between CTGF concentration in nasal mucosa and dacryocystorhinostomy outcome, which supports the hypothesis suggested by several authors linking dacryocystorhinostomy failure with chronic inflammation in nasal mucosa.
Subject(s)
Dacryocystorhinostomy , Cytokines , Fibrosis , Humans , Inflammation , Transforming Growth Factor betaABSTRACT
OBJECTIVE: To investigate the impact of the nasal mucosa on the outcomes of dacryocystorhinostomy on the basis of morphologic findings. MATERIAL AND METHODS: The investigation enrolled 73 patients who had undergone endonasal endoscopic dacryocystorhinostomy. Nasal mucosal biopsies were intraoperatively taken from all the patients. The obtained samples were subjected to standard histological examination, as well as to immunohistochemical study using an anti-alpha-smooth muscle actin antibody. To determine the intensity of inflammation in the tissue sample, a chronic inflammation score was calculated. The cell elements positively stained with α-smooth muscle actin were estimated using a semi-automatic method. The patients were divided into groups in accordance with the outcome of surgical treatment after 6 months. RESULTS: An unfavorable outcome of dacryocystorhinostomy was observed in 10 (13.7%) patients. The samples obtained from the patients showed a higher chronic inflammation score (8.33%) and a larger number of the cell elements positively stained with α-smooth muscle actin (6026.38±1944.29). The correlation between the outcome of surgical intervention and the quantitative characteristics of myofibroblasts was statistically significant (p<0.05). CONCLUSION: These studies suggest that there is a direct correlation of the efficiency of endonasal endoscopic dacryocystorhinostomy with the presence and degree of chronic nasal mucosal inflammation at baseline.
Subject(s)
Dacryocystorhinostomy , Inflammation , Nasal Mucosa , Biopsy , Chronic Disease , Endoscopy , Humans , Nasal Mucosa/pathology , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: 3-Hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, which stimulates muscle fatty acid uptake, has been implicated in the pathogenesis of insulin resistance. We tested the hypothesis that circulating 3-HIB herald insulin resistance and that metabolic improvement with weight loss are related to changes in BCAAs and 3-HIB. METHODS AND RESULTS: We analyzed plasma and urine in 109 overweight to obese individuals before and after six months on hypocaloric diets reduced in either carbohydrates or fat. We calculated the homeostasis model assessment index (HOMA-IR) and whole body insulin sensitivity from oral glucose tolerance tests and measured intramyocellular fat by magnetic resonance spectroscopy. BCAAs and 3-HIB plasma concentrations were inversely related to insulin sensitivity but not to intramyocellular fat content at baseline. With 7.4 ± 4.5% weight loss mean BCAA and 3-HIB plasma concentrations did not change, irrespective of dietary macronutrient content. Individual changes in 3-HIB with 6-month diet but not BCAAs were correlated to the change in whole body insulin sensitivity and HOMA-IR independently of BMI changes. CONCLUSIONS: 3-HIB relates to insulin sensitivity but is not associated with intramyocellular fat content in overweight to obese individuals. Moreover, changes in 3-HIB rather than changes in BCAAs are associated with metabolic improvements with weight loss. Registration number for clinical trials: ClinicalTrials.gov Identifier: NCT00956566.
Subject(s)
Amino Acids, Branched-Chain/blood , Caloric Restriction , Diet, Carbohydrate-Restricted , Diet, Fat-Restricted , Hydroxybutyrates/blood , Insulin Resistance , Obesity/diet therapy , Weight Loss , Adipose Tissue/metabolism , Adult , Biomarkers/blood , Blood Glucose/metabolism , Female , Glucose Tolerance Test , Humans , Insulin/blood , Magnetic Resonance Spectroscopy , Male , Metabolomics/methods , Middle Aged , Muscle, Skeletal/metabolism , Obesity/blood , Obesity/diagnosis , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Amino acids may interfere with insulin action, particularly in obese individuals. We hypothesized that increased circulating branched-chain and aromatic amino acids herald insulin resistance and ectopic fat storage, particularly hepatic fat accumulation. METHODS AND RESULTS: We measured fasting branched-chain and aromatic amino acids (tryptophan, tyrosine, and phenylalanine) by mass spectrometry in 111 overweight to obese subjects. We applied abdominal magnetic resonance imaging and spectroscopy to assess adipose tissue distribution and ectopic fat storage, respectively. Plasma branched-chain amino acids concentrations were related to insulin sensitivity and intrahepatic fat independent from adiposity, age and gender, but not to abdominal adipose tissue or intramyocellular fat. CONCLUSIONS: In weight stable overweight and obese individuals, branched-chain amino acid concentrations are specifically associated with hepatic fat storage and insulin resistance.
Subject(s)
Adiposity , Amino Acids, Aromatic/blood , Amino Acids, Branched-Chain/blood , Dietary Proteins/blood , Insulin Resistance , Liver/metabolism , Obesity/blood , Adult , Biomarkers/blood , Blood Glucose/metabolism , Cross-Sectional Studies , Female , Germany , Humans , Insulin/blood , Liver/diagnostic imaging , Liver/physiopathology , Magnetic Resonance Imaging , Male , Mass Spectrometry , Metabolomics/methods , Middle Aged , Obesity/diagnostic imaging , Obesity/diet therapy , Obesity/physiopathologyABSTRACT
Blast injuries may result from a variety of causes but the biomechanical impact and pathophysiological consequences do not differ between domestic or industrial accidents or even terrorist attacks. However, this differentiation relevantly affects the tactical procedures of the rescue teams. Focusing on further detonations, top priority is given to the personal safety of all rescue workers. The rareness of blast injuries in a civilian setting results in a lack of experience on the one hand but on the other hand the complexity of blast injuries to the human body places high demands on the knowledge and skills of the entire rescue team for competent treatment. The purpose of this article is to explain the physicochemical principles of explosions and to convey tactical and medical knowledge to emergency medical services.
Subject(s)
Blast Injuries/therapy , Emergency Medical Services , Head Injuries, Penetrating/therapy , Humans , Mass Casualty Incidents , TerrorismABSTRACT
Introduction: In 2002, gynecology residents in North Rhine-Westfalia (NRW) were asked how satisfied they were with their working and training conditions. A new extended survey of gynecology residents aimed to evaluate whether changes to specialist training regulations had affected residents' levels of job satisfaction and to identify areas where training conditions still urgently required improvement. Material and Methods: A total of 1223 questionnaires with 52 questions were sent to the 159 gynecology clinics in NRW. Responses could be dichotomous, multi-level or quantitative. The results were analyzed with regard to age, gender, family status and type of clinic and were additionally compared with the results of a previous survey. Results: The percentage of women residents has increased to 84.6â%. A workload of more than 48 hours per week has resulted in decreased motivation and lower levels of satisfaction during training, although overall levels of satisfaction have clearly improved compared to the previous survey. Use of a logbook to create a more structured training program has not achieved the desired effect. Nevertheless, seven of eight gynecology residents would study medicine again, although 28â% of the budding gynecologists are considering working abroad or in private industry. Conclusion: Both training and overall satisfaction with working conditions must be improved to preserve the appeal of gynecology for young academics. This survey aims to identify key factors which are responsible for (dis)satisfaction with working conditions.
ABSTRACT
INTRODUCTION: Radical resection of deep infiltrating endometriosis (DIE), including bladder and bowel resection, provides relief from pain in symptomatic patients. The laparoscopic approach to treatment is well established for bowel resection but normally requires additional abdominal incisions for specimen retrieval. Here we describe our technique of laparoscopically assisted rectal resection and transvaginal specimen retrieval (LARRT) and provide follow-up information on pain scores and complications. MATERIALS AND METHODS: Retrospective observational monocentric study on all DIE patients with rectal infiltration treated between 2008 and 2010 with LATRR at our department. Follow-up was obtained for at least 3 years, including baseline 1-year and 3-year pain scores. RESULTS: We identified four patients undergoing LARRT available for follow-up. DIE was confirmed by histology in all cases. There were no intraoperative complications. Two patients had transient postoperative urinary retention, one patient developed recto-vaginal fistula and required transient colostomy. One patient suffered from persistent vaginal dryness. All patients, however, reported persistent pain relief, including at the end of follow-up period. CONCLUSION: LARRT is a feasible variation of laparoscopic bowel resection for DIE with rectal infiltration. In our study it has promising results with respect to pain control. Larger studies will, however, be required to determine the safety of this procedure.
Subject(s)
Endometriosis/surgery , Laparoscopy/methods , Rectal Diseases/surgery , Uterine Diseases/surgery , Adult , Colpotomy , Endometriosis/pathology , Feasibility Studies , Female , Follow-Up Studies , Humans , Medical Illustration , Photography , Postoperative Complications , Rectal Diseases/pathology , Retrospective Studies , Uterine Diseases/pathologyABSTRACT
BACKGROUND: The aim of this paper was to determine the influence of different in vitro culture media on mRNA expression of Hedgehog genes, il-6, and important genes regarding reactive oxygen species in single mouse embryos. METHODS: Reverse transcription of single embryos either cultured in vitro from day 0.5 until 3.5 (COOK's Cleavage medium or Vitrolife's G-1 PLUS medium) or in vivo until day 3.5 post coitum. PCR was carried out for ß-actin followed by nested-PCR for shh, ihh, il-6, nox, gpx4, gpx1, and prdx2. RESULTS: The number of murine blastocysts cultured in COOK medium which expressed il-6, gpx4, gpx1, and prdx2 mRNA differed significantly compared to the in vivo group. Except for nox, the mRNA profile of the Vitrolife media group embryos varied significantly from the in vivo ones regarding the number of blastocysts expressing the mRNA of shh, ihh, il-6, gpx4, gpx1 and prdx2. CONCLUSIONS: The present study shows that different in vitro culture media lead to different mRNA expression profiles during early development. Even the newly developed in vitro culture media are not able to mimic the female reproductive tract. The question of long-term consequences for children due to assisted reproduction techniques needs to be addressed in larger studies.
Subject(s)
Blastocyst , Hedgehog Proteins/genetics , Interleukin-6/genetics , RNA, Messenger/genetics , Reactive Oxygen Species/metabolism , Animals , Base Sequence , Culture Media , DNA Primers , Female , In Vitro Techniques , Mice , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND: Novel therapeutic approaches for endometriosis based on molecular strategies may prove to be useful. Conditionally replicative adenoviruses (CRAds) are designed to exploit key differences between target and normal cells. The wild-type adenovirus (Adwt) promoter can be replaced by tissue-specific promoters, allowing viral replication only in target cells. Viral infectivity can be enhanced by altering Ad tropism via fiber modification. We investigated whether CRAds can be used to target endometriosis and determined the most efficient transcriptional- and transductional-targeting strategy. METHODS: An in vitro study was carried out using human endometriotic cell lines, 11Z (epithelial) and 22B (stromal), normal human ovarian surface epithelial cell line (NOSE006) and primary human endometriosis cells. A total of 9 promoters and 12 Ad tropism modifications were screened by means of a luciferase reporter assay. From this screening data, three CRAds (CRAd-S-pK7, CRAd-S-RGD, CRAd-S-F5/3sigma1, all incorporating the survivin promoter but with different fiber modifications) were selected to perform experiments using Adwt and a replication-deficient virus as controls. CRAds were constructed using a plasmid recombination system. Viral-binding capacity, rates of entry and DNA replication were evaluated by quantitative real-time PCR of viral genome copy. Cell-killing effects were determined by crystal violet staining and a cell viability assay for different concentrations of viral particles per cell. RESULTS: Comparison of promoters demonstrated that the survivin promoter exhibited the highest induction in both endometriotic cell lines. Among the fiber-modified viruses, the polylysine modification (pK7) showed the best infection enhancement. CRAd-S-pK7 was validated as the optimal CRAd to target endometriosis in terms of binding ability, entry kinetics, DNA replication and cell-killing effect. CRAd-S-pK7 also exhibited a high level of DNA replication in primary endometriosis cells. CONCLUSIONS: CRAd-S-pK7 has the best infection and cell-killing effect in the context of endometriosis. It could prove to be a useful novel method to target refractory cases of endometriosis.
Subject(s)
Adenoviridae/genetics , Endometriosis/therapy , Virus Replication , Cell Line , Endometriosis/genetics , Female , Humans , Promoter Regions, Genetic , Virus Attachment , Virus Replication/geneticsABSTRACT
The Centers for Disease Control and Prevention (CDC) recommends hepatitis B surface antigen (HBsAg) testing to identify hepatitis B virus (HBV) infection for foreign-born persons from areas with HBsAg prevalence of > or = 2%. Currently, most HBsAg screening in the United States is performed by independent community organizations. For these HBsAg screening programs, we collected information about the location, number of people screened, other services beyond screening provided, the population/ethnicity groups targeted for screening, and the prevalence of HBsAg among those screened. We identified programs offering screening by contacting programs known to us, from interviews with identified programs, and from structured Internet searches, and collected information using a simple e-mail survey with follow-up phone calls. We identified 55 possible community HBsAg screening programs, of which we successfully contacted 31 programs. In the past year, contacted programs screened an estimated 21 817 patients with an 8.1% average HBsAg prevalence. The majority of programs screened persons born in Asia and their children, and a small number of programs screened persons from Africa or Eastern Europe; very few programs screened U.S.-born persons at risk of HBV infection due to behavioural factors. We identified few or no programs in the American Southeast, the Midwest, and the Southwest outside of California and the Houston area. The HBsAg screening programs that we contacted were effective in identifying and screening patients at risk of HBV as evidenced by the high prevalence observed among those screened. However, their efforts alone are likely insufficient to meet the need for screening recommended by CDC.
Subject(s)
Health Services Research , Hepatitis B Surface Antigens/blood , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Mass Screening/statistics & numerical data , Humans , Prevalence , United States/epidemiologyABSTRACT
Whereas virotherapy has emerged as a novel and promising approach for neoplastic diseases, appropriate model systems have hampered preclinical evaluation of candidate conditionally replicative adenovirus agents (CRAds) with respect to liver toxicity. This is due to the inability of human viral agents to cross species. We have recently shown the human liver tissue slice model to be a facile means to validate adenoviral replication. On this basis, we sought to determine whether our ex vivo liver tissue slice model could be used to assess CRAd-mediated liver toxicity. We analyzed and compared the toxicity of a conditionally replicative adenovirus (AdDelta24) to that of a replication incompetent adenovirus (Adnull [E1-]) in mouse and human liver tissue slices. To accomplish this, we examined the hepatic apoptosis expression profile by DNA microarray analyses, and compared these results to extracellular release of aminotransferase enzymes, along with direct evidence of apoptosis by caspase-3 immunhistochemical staining and TUNEL assays. Human and mouse liver tissue slices demonstrated a marked increase in extracellular release of aminotransferase enzymes on infection with AdDelta24 compared to Adnull. AdDelta24-mediated liver toxicity was further demonstrated by apoptosis induction, as detected by caspase-3 immunohistochemical staining, TUNEL assay and microarray analysis. In conclusion, concordance of CRAd-mediated apoptosis in both the human and the mouse liver tissue slice models was demonstrated, despite the limited replication ability of CRAds in mouse liver slices. The results of this study, defining the CRAd-mediated apoptosis gene expression profiles in human and mouse liver, may lay a foundation for preclinical liver toxicity analysis of CRAd agents.
Subject(s)
Adenoviridae/genetics , Apoptosis , Genetic Vectors , Liver Neoplasms/virology , Liver/virology , Virus Replication , Animals , Biological Assay , Down-Regulation , Gene Deletion , Humans , Liver/cytology , Mice , Microarray Analysis , Models, Biological , Reverse Transcriptase Polymerase Chain Reaction , Up-RegulationABSTRACT
Adenoviruses (Ads) are efficient gene transfer vehicles, but Ad-mediated gene therapy for ovarian cancer remains limited in vivo by inefficient and nonspecific gene transfer. Mesothelin (MSLN), a cell surface glycoprotein, is overexpressed in ovarian cancer but not in normal tissues except mesothelial cells. Therefore, MSLN is an attractive candidate for transcriptional and transductional targeting in the context of ovarian cancer gene therapy. We evaluated the expression of MSLN mRNA and MSLN surface protein in ovarian cancer cells. Ads containing the MSLN promoter driving reporter gene expression were created and tested in ovarian cancer cell lines and purified ovarian cancer cells isolated from patients. To evaluate transductional targeting, we used an Ad vector containing an Fc-binding domain within the fiber protein, which served as a docking domain for binding with anti-MSLN immunoglobulins. Both RT-PCR and flow cytometry revealed high MSLN gene and protein expression in ovarian cancer cells. The MSLN promoter was activated in ovarian cancer cells, but showed significantly reduced activity in normal control cells. Transductional targeting of Ads via anti-MSLN antibody increased transgene expression in ovarian cancer cells. This report describes the use of MSLN for transcriptional as well as transductional targeting strategies for ovarian cancer gene therapy.
Subject(s)
Genetic Therapy/methods , Membrane Glycoproteins/genetics , Ovarian Neoplasms/therapy , Promoter Regions, Genetic , Adenoviridae/genetics , Cell Line , Cell Line, Tumor , Female , GPI-Linked Proteins , Gene Expression , Gene Targeting , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Humans , Membrane Glycoproteins/analysis , Mesothelin , RNA, Messenger/analysis , Transduction, Genetic/methods , Tumor Cells, CulturedABSTRACT
INTRODUCTION: There has been renewed interest in mushroom medicinal properties. We studied cholesterol lowering properties of Ganoderma lucidum (Gl), a renowned medicinal species. RESULTS: Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did not effect LDL; but decreased total cholesterol (TC) 9.8%, and HDL 11.2%. Gl (2.5 and 5%) had effects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC, LDL- and HDL cholesterol 20, 27, and 18%, respectively (P < 0.05); increased fecal cholestanol and coprostanol; and decreased cholate. CONCLUSIONS: Overall, Gl has potential to reduce LDL cholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components in lipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine human cholesterol lowering properties. Innovative new cholesterol-lowering foods and medicines containing Gl are envisioned.
ABSTRACT
BACKGROUND: It is well known that the acceptance of the fetoplacental unit in human pregnancy requires maternal immune tolerance, which is thought to be regulated locally by the placenta. Therefore an anti-inflammatory cytokine such as IL-10 plays a critical role in different pregnancy disorders including preeclampsia. In the present study, we examined the expression of both proinflammatory (TNF-alpha, IL-1beta, IL-2) and immunoregulatory (IL-6, IL-10) cytokines from normal term and preeclamptic patients in human trophoblast cultures. METHODS: Eleven patients with preeclampsia and 11 patients with a normal pregnancy at term were included in the study. Trophoblast cells isolated from placentas were cultured up to 48 h under standard tissue culture conditions and cytokine release was determined by ELISA. IL-10 synthesis was significantly decreased in the third trimester in preeclamptic patients in comparison with the control group. RESULTS: There were no significant differences in IL-1beta, IL-2, IL-6 or TNF-alpha expression but a significant alteration in IL-10 release in trophoblast cultures in vitro in term placentas from preeclamptic patients compared with normal pregnancy. CONCLUSIONS: Because IL-10 is a potent regulator of anti-inflammatory immune response these abnormalities may be associated with the inadequate placental development in preeclampsia.
Subject(s)
Cytokines/metabolism , Interleukin-10/deficiency , Pre-Eclampsia/physiopathology , Trophoblasts/metabolism , Adolescent , Adult , Analysis of Variance , Blood Pressure/physiology , Cells, Cultured , Female , Humans , Interleukin-1/metabolism , Interleukin-10/metabolism , Interleukin-2/metabolism , Interleukin-6/metabolism , Pre-Eclampsia/metabolism , Pregnancy , Pregnancy Trimester, Third/physiology , Proteinuria/urine , Trophoblasts/cytology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
PURPOSE: Interactions of hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) have been proposed as being important in promoting tumour progression and dissemination. This comparative study was designed to investigate the RHAMM expression patterns in endometrial carcinoma. METHODS: We examined a series of 89 endometrial carcinomas and 15 normal endometrial tissues by immunohistochemistry, using a RHAMM-specific polyclonal antibody. Expression of RHAMM was assessed according to the pattern and intensity within (overall cytoplasm, center/periphery of tumours) and between the tumours. The staining results were compared to the corresponding clinical data (age, menopause status, histological staining, histological grading, lymph node status). RESULTS: RHAMM-expression was detectable in 58% of the 89 tumours [Histological stage: pT1a (8/12); pT1b (16/37); pT1c (18/26); pT2 (6/9); pT3a (4/5)] and 13% (2/15) of the normal endometrial tissues. The positivity rates for RHAMM were 100% in patients with positive lymph nodes but only 50.7% in patients with negative lymph nodes ( P<0-01). Additionally, the expression pattern showed a highly significant correlation ( P<0.01) with the histological grade of the tumours [G1 (6/42), G2 (33/34), G3 (13/13)] and occurrence of lymph node metastases. CONCLUSIONS: Our results suggest that RHAMM expression may enhance and improve the invasion and metastasis of endometrial carcinomas.
Subject(s)
Endometrial Neoplasms/metabolism , Extracellular Matrix Proteins/metabolism , Hyaluronan Receptors/metabolism , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Papillary/metabolism , Adenocarcinoma, Papillary/pathology , Carcinosarcoma/metabolism , Carcinosarcoma/pathology , Case-Control Studies , Cell Division , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/pathology , Endometrium/metabolism , Female , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Prognosis , Survival RateABSTRACT
OBJECTIVE: The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated doses (MTDs) of a docetaxel-carboplatin regimen in patients with locally advanced cervical cancer (LACC) or recurrent cervical cancer. The regimen was administered weekly, with a maximum of 12 courses. PATIENTS AND METHODS: Twenty patients were treated with with a total of 145 cycles of weekly carboplatin and docetaxel. The starting dose of docetaxel was 25 mg/m(2) with increments of 5 mg/m(2) until a final dose of 35 mg/m(2) was reached. Dose-escalation of docetaxel was followed by carboplatin at AUC 2, AUC 2.5, and AUC 3, respectively. Defined dose-limiting toxicities were WHO grade (G) 3 hematotoxicity, G4 mucositis, and G2 neurotoxicity. The response status of the patients was assessed using the common ECOG response criteria. RESULTS: Two of four patients developed a DLT at dose level 4. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. The MTD was reached at docetaxel 35 mg/m(2) and carboplatin AUC 2 mg/mL.min. The overall response rate was 65% in the entire group of evaluable patients and 77% in patients with primary LACC, with two cases of pathological complete response. CONCLUSION: This dose-dense regimen was well-tolerated and could be administered on an outpatient basis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Uterine Cervical Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carboplatin/adverse effects , Docetaxel , Drug Administration Schedule , Female , Hematologic Diseases/chemically induced , Humans , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effectsABSTRACT
For many decades, invasive cervical cancer has been considered more or less chemoresistant and chemotherapy has been limited to patients presenting with overt metastatic disease or those suffering from pelvic recurrences which could not be advised to secondary local treatments. However, more than 20 different single agents are considered active in cervical cancer. Recent cooperative clinical trials have demonstrated the superiority of multi-modality strategies for patients with high-risk cervical cancer. These studies integrating chemotherapy as part of the primary therapeutic concept have provided the most significant improvement of locally advanced disease in more than three decades. This review summarizes current standards of chemotherapy for invasive cervical cancer and shows new developments which may improve systemic treatment of the disease.
Subject(s)
Antineoplastic Agents/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Female , Humans , Neoplasm Invasiveness , Survival Rate , Treatment Outcome , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/radiotherapySubject(s)
Adnexal Diseases/surgery , Laparoscopy/methods , Pregnancy Complications/surgery , Pregnancy Outcome , Abdomen, Acute/diagnostic imaging , Abdomen, Acute/surgery , Adnexal Diseases/diagnostic imaging , Adult , Cesarean Section , Female , Humans , Minimally Invasive Surgical Procedures/methods , Pneumoperitoneum, Artificial , Pregnancy , Pregnancy Complications/diagnostic imaging , Pregnancy Trimester, First , Pregnancy, Multiple , Torsion Abnormality/diagnostic imaging , Torsion Abnormality/surgery , Treatment Outcome , Twins , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. STUDY DESIGN: Two prospective open-label studies with longitudinal follow-up in the second trial. SETTING: Academic Department of Obstetrics and Gynecology, University of Cologne. PATIENTS: Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. MAIN OUTCOME MEASURE: Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. RESULTS: Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. CONCLUSION: Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.