ABSTRACT
Subject(s)
Aged , Female , Humans , Comorbidity , Cytoreduction Surgical Procedures , Diagnosis , Drug Therapy , Follow-Up Studies , Methods , Neoadjuvant Therapy , Ovarian Neoplasms , Patient Preference , Proportional Hazards Models , Prospective StudiesABSTRACT
Ovarian cancer is the eighth most frequent cancer in women and is the most lethal gynecologic malignancy worldwide. The majority of ovarian cancer patients are newly diagnosed presenting with advanced-stage disease. Primary cytoreductive surgery and adjuvant taxane- and platinum-based combination chemotherapy are the standard treatment for advanced ovarian cancer. A number of studies have consistently shown that successful cytoreductive surgery and the resultant minimal residual disease are significantly associated with survival in patients with this disease. Much has been written and even more debated regarding the competing perspectives of biology of ovarian cancer versus the value of aggressive surgical resection. This review will focus on the current evidences and outcomes supporting the positive impact of aggressive surgical effort on survival in the primary management of ovarian cancer.
Subject(s)
Female , Humans , Cytoreduction Surgical Procedures/methods , Evidence-Based Medicine , Neoplasm, Residual/surgery , Observer Variation , Ovarian Neoplasms/surgery , Practice Patterns, Physicians' , Randomized Controlled Trials as Topic , Retrospective StudiesABSTRACT
OBJECTIVE: To determine which computed tomography (CT) imaging features predict pleural malignancy in patients with advanced epithelial ovarian carcinoma (EOC) using video-assisted thoracic surgery (VATS), pathology, and cytology findings as the reference standard. METHODS: This retrospective study included 44 patients with International Federation of Obstetrics and Gynecology (FIGO) stage III or IV primary or recurrent EOC who had chest CT < or =30 days before VATS. Two radiologists independently reviewed the CT studies and recorded the presence and size of pleural effusions and of ascites; pleural nodules, thickening, enhancement, subdiaphragmatic tumour deposits and supradiaphragmatic, mediastinal, hilar, and retroperitoneal adenopathy; and peritoneal seeding. VATS, pathology, and cytology findings constituted the reference standard. RESULTS: In 26/44 (59%) patients, pleural biopsies were malignant. Only the size of left-sided pleural effusion (reader 1: rho=-0.39, p=0.01; reader 2: rho=-0.37, p=0.01) and presence of ascites (reader 1: rho=-0.33, p=0.03; reader 2: rho=-0.35, p=0.03) were significantly associated with solid pleural metastasis. Pleural fluid cytology was malignant in 26/35 (74%) patients. Only the presence (p=0.03 for both readers) and size (reader 1: rho=0.34, p=0.04; reader 2: rho=0.33, p=0.06) of right-sided pleural effusion were associated with malignant pleural effusion. Interobserver agreement was substantial (kappa=0.78) for effusion size and moderate (kappa=0.46) for presence of solid pleural disease. No other CT features were associated with malignancy at biopsy or cytology. CONCLUSION: In patients with advanced EOC, ascites and left-sided pleural effusion size were associated with solid pleural metastasis, while the presence and size of right-sided effusion were associated with malignant pleural effusion. No other CT features evaluated were associated with pleural malignancy.
Subject(s)
Humans , Ascites , Biopsy , Gynecology , Neoplasm Metastasis , Obstetrics , Ovarian Neoplasms , Pleural Diseases , Pleural Effusion , Pleural Effusion, Malignant , Pleural Neoplasms , Retrospective Studies , Seeds , Thoracic Surgery, Video-Assisted , ThoraxABSTRACT
The surgical management of advanced epithelial ovarian cancer involves cytoreduction, or removal of grossly-evident tumor. Residual disease after surgical cytoreduction of ovarian cancer has been shown to be strongly associated with survival. The goal of surgery is "optimal" surgical cytoreduction, which is generally defined as residual disease of 1 cm or less. However, the designation of "optimal" surgical cytoreduction has evolved to include maximal surgical effort and no gross residual disease. In order to achieve this, more aggressive surgical procedures such as rectosigmoidectomy, diaphragm peritonectomy, partial liver resection, and video-assisted thoracic surgery are reported and increasingly utilized in the surgical management of advanced ovarian cancer. The role of maximal surgical effort also extends to the recurrent setting where the goal of surgery should be complete cytoreduction. Patient selection is important in identifying appropriate candidates for surgical cytoreduction in the recurrent setting. The purpose of this article is to review the role of maximum surgical effort in primary and recurrent ovarian cancer.
Subject(s)
Diaphragm , Liver , Neoplasms, Glandular and Epithelial , Ovarian Neoplasms , Patient Selection , Thoracic Surgery, Video-AssistedABSTRACT
The purpose of this study was to examine the effects of glutathione (GSH) depletion and cellular oxidation on rat diaphragm contractility and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) function in vitro under basal conditions and following fatiguing stimulation. Buthionine sulfoximine (BSO) treatment (n = 10) for 10 days (20 mM in drinking water) reduced (P < 0.05) diaphragm GSH content (nmol/mg protein) and the ratio of GSH to glutathione disulfide (GSH/GSSG) by 91% and 71%, respectively, compared with controls (CTL) (n = 10). Western blotting showed that Hsp70 expression in diaphragm was not increased (P > 0.05) with BSO treatment. As hypothesized, basal peak twitch force (g/mm(2)) was increased (P < 0.05), and fatigability in response to repetitive stimulation (350-ms trains at 100 Hz once every 1 s for 5 min) was also increased (P < 0.05) in BSO compared with CTL. Both Ca(2+) uptake and maximal SERCA activity (mumol.g protein(-1).min(-1)) measured in diaphragm homogenates that were prepared at rest were increased (P < 0.05) with BSO treatment, an effect that could be partly explained by a twofold increase (P < 0.05) in SERCA2a expression with BSO. In response to the 5-min stimulation protocol, both Ca(2+) uptake and maximal SERCA activity were increased (P < 0.05) in CTL but not (P > 0.05) in BSO diaphragm. We conclude that 1) cellular redox state is more optimal for contractile function and fatigability is increased in rat diaphragm following BSO treatment, 2) SERCA2a expression is modulated by redox signaling, and 3) regulation of SERCA function in working diaphragm is altered following BSO treatment.
Subject(s)
Antioxidants/metabolism , Buthionine Sulfoximine/pharmacology , Diaphragm/drug effects , Enzyme Inhibitors/pharmacology , Glutathione/metabolism , Muscle Contraction/drug effects , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sarcoplasmic Reticulum/drug effects , Animals , Calcium/metabolism , Diaphragm/enzymology , Diaphragm/metabolism , Electric Stimulation , Glutamate-Cysteine Ligase/antagonists & inhibitors , Glutamate-Cysteine Ligase/metabolism , HSP70 Heat-Shock Proteins/metabolism , Kinetics , Male , Muscle Fatigue/drug effects , Muscle Strength/drug effects , Oxidation-Reduction , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Sarcoplasmic Reticulum/enzymology , Sarcoplasmic Reticulum/metabolism , Signal Transduction/drug effects , Up-RegulationABSTRACT
The inhalation of flour dust has been implicated in the induction of sensitisation and elicitation of respiratory symptoms, such as asthma in bakers. In addition to the cereal allergens present in wheat flour, enzymes in flour improvers, in particular fungal alpha-amylase, are now known to be a significant cause of respiratory allergy in the baking industry.A monoclonal antibody based enzyme-linked immunoassay (ELISA) was developed using two monoclonal antibodies that recognised two distinct epitopes of the fungal alpha-amylase enzyme. The ELISA had an inter-assay variation of 12.0% at 1360 pg/ml and 12.8% at 564 pg/ml and intra-assay variation of 4.9% at 1340 pg/ml and 6.1% at 504 pg/ml. The assay had a sensitivity of 200 pg/ml. Competitive inhibition assays confirmed that the monoclonal antibodies had no cross reactivity with other enzymes used in the baking industry and could distinguish added fungal alpha-amylase from cereal amylase. We assessed the levels of exposure to dust, total protein and fungal alpha-amylase in four UK bakeries ranging in size and technical capabilities. Within the bakeries we surveyed, workers were exposed to variable levels of inhalable dust (0.8-39.8 mg/m3), total protein (0-5.7 mg/m3) and fungal alpha-amylase (0-29.8 ng/m3). Consecutive 15 min personal samples taken over a 1 h period demonstrated that the ELISA could measure fungal alpha-amylase exposure in such a 15 min period. Short term peak exposures to fungal alpha-amylase could be identified which may contribute to the sensitisation in individuals who appear to have low exposure levels if measured over a full shift period.
Subject(s)
Antibodies, Monoclonal , Environmental Monitoring/methods , Flour/microbiology , Fungal Proteins/analysis , alpha-Amylases/analysis , England , Food-Processing Industry , Humans , Sensitivity and SpecificityABSTRACT
OBJECTIVE: In vitro treatment with ultraviolet B (UVB) induces relocalization of lupus autoantigens to the cell surface. We have addressed the relationship between autoantigen relocalization, accumulation of intracellular reactive oxygen species (ROS) and the induction of apoptosis following UVA and UVB exposure. METHODS: Human primary keratinocytes were exposed in vitro to doses of UVA and UVB equivalent to 0.01-4 times the minimal erythemal dose. The cellular locations of Ro60, Ro52, Sm, U2-B" and La were determined using monoclonal antibodies. ROS accumulation and apoptosis induction were assessed using the intracellular ROS probe 2'7'-dichlorodihydrofluorescein diacetate, and the viability stains Hoechst 33342 and propidium iodide. RESULTS: UV treatment induced the relocalization of all five autoantigens investigated and an accumulation of ROS. UVA and UVB induced necrosis and apoptosis, respectively. CONCLUSION: These data suggest that both UVA and UVB induce ROS within keratinocytes but have significantly different effects upon autoantigen relocalization and cell viability.
