Improving quality and safety in paediatric spinal surgery: the team approach.

Aims: The aim of this study was to evaluate improvements in the quality and safety of paediatric spinal surgery following the implementation of a specialist Paediatric Spinal Surgical Team (PSST) in the operating theatre. Patients and Methods: A retrospective consecutive case study of paediatric spinal operations before (between January 2008 and December 2009), and after (between January 2012 and December 2013) the implementation of PSST, was performed. A comparative analysis of outcome variables including surgical site infection (SSI), operating time (ORT), blood loss (BL), length of stay (LOS), unplanned staged procedures (USP) and transfusion rates (allogenic and cell-saver) was performed between the two groups. The rate of complications during the first two postoperative years was also compared between the groups. Results: There were 130 patients in the pre-PSST group and 277 in the post-PSST group. The age, gender, body mass index (BMI), preoperative Cobb angle of the major curve and the number of levels involved were similar between the groups. There were statistically significant differences in SSI, ORT, LOS, allogenic blood transfusion volume (ABTV), and USPs between the groups. There was a 94% decrease in the rate of SSI's in the post-PSST group. Patients in the post-PSST group had a mean reduction in ORT of 53 minutes (sd 7.7) (p = 0.013), LOS by 5.4 days (sd 1.8) (p = 0.019), and ABTV by 226.3 ml (sd 28.4) (p < 0.001). There were significantly more USPs in the pre-PSST group (6.2%) compared with the post-PSST group (2.9%) (p = 0.001). Multivariate regression showed that the effect of PSST remained significant for ORT, LOS, BL, ABVT and cell-saver amount transfused (p = 0.0001). The odds of having a SSI were tenfold higher and the odds of receiving a blood transfusion were 2.4 times higher, respectively, in the pre-PSST group (p = 0.004 and p = 0.011). The rate of complications within the first two postoperative years was significantly higher in the pre-PSST group (13.1%) compared with the post-PSST group (4.3%) (p < 0.001). Conclusion: The implementation of a PSST in the operating theatre significantly improves the outcomes in paediatric spinal surgery. Cite this article: Bone Joint J 2018;100-B:493-8.

Chronic treatment with a stable obestatin analog significantly alters plasma triglyceride levels but fails to influence food intake; fluid intake; body weight; or body composition in rats.

Obestatin (OB(1-23) is a 23 amino acid peptide encoded on the preproghrelin gene, originally reported to have metabolic actions related to food intake, gastric emptying and body weight. The biological instability of OB(1-23) has recently been highlighted by studies demonstrating its rapid enzymatic cleavage in a number of biological matrices. We assessed the stability of both OB(1-23) and an N-terminally PEGylated analog (PEG-OB(1-23)) before conducting chronic in vivo studies. Peptides were incubated in rat liver homogenate and degradation monitored by LC-MS. PEG-OB(1-23) was approximately 3-times more stable than OB(1-23). Following a 14 day infusion of Sprague-Dawley rats with 50 nmol/kg/day of OB(1-23) or a N-terminally PEGylated analog (PEG-OB(1-23)), we found no changes in food/fluid intake, body weight and plasma glucose or cholesterol between groups. Furthermore, morphometric liver, muscle and white adipose tissue (WAT) weights and tissue triglyceride concentrations remained unaltered between groups. However, with stabilized PEG-OB(1-23) we observed a 40% reduction in plasma triglycerides. These findings indicate that PEG-OB(1-23) is an OB(1-23) analog with significantly enhanced stability and suggest that obestatin could play a role in modulating physiological lipid metabolism, although it does not appear to be involved in regulation of food/fluid intake, body weight or fat deposition.

Effects of sub-chronic exposure to naturally occurring N-terminally truncated metabolites of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), GIP(3-42) and GLP-1(9-36)amide, on insulin secretion and glucose homeostasis in ob/ob mice.

Glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important enteroendocrine hormones that are rapidly degraded by an ubiquitous enzyme dipeptidyl peptidase IV to yield truncated metabolites GIP(3-42) and GLP-1(9-36)amide. In this study, we investigated the effects of sub-chronic exposure to these major circulating forms of GIP and GLP-1 on blood glucose control and endocrine pancreatic function in obese diabetic (ob/ob) mice. A once daily injection of either peptide for 14 days had no effect on body weight, food intake or pancreatic insulin content or islet morphology. GLP-1(9-36)amide also had no effect on plasma glucose homeostasis or insulin secretion. Mice receiving GIP(3-42) exhibited small but significant improvements in non-fasting plasma glucose, glucose tolerance and glycaemic response to feeding. Accordingly, plasma insulin responses were unchanged suggesting that the observed enhancement of insulin sensitivity was responsible for the improvement in glycaemic control. These data indicate that sub-chronic exposure to GIP and GLP-1 metabolites does not result in physiological impairment of insulin secretion or blood glucose control. GIP(3-42) might exert an overall beneficial effect by improving insulin sensitivity through extrapancreatic action.

The effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington between January 1990 and January 2000 were eligible; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 33 months (range, 1 to 120 months). RESULTS: Age was < 45 years in 15% of patients, between 46 and 64 years in 47% of patients, and > 65 years in 38% of patients. Younger patients were statistically more obese than older patients (Body Mass Index of 40.3 kg/m2 vs. 35.3 kg/m2 vs. 31.0 kg/m2, P < 0.001). Intraoperatively, there were no differences between the three groups in the percentage of patients with lymph node sampling, operative time, blood loss, or complications. Postoperatively, older patients had more wound infections (P = 0.002), more cardiac events (P = 0.001), and more episodes of ileus (P = 0.025). Evaluation of pathology revealed that patients < 45 years old were statistically more likely to have endometrioid histology, grade I tumors, and stage IA disease. Women over age 65 were significantly more likely to have papillary serous histology, grade 3 tumors, and stage IC as compared to the younger patients. A subset analysis of patients > 75 years of age showed an increase in the percentage of patients with papillary serous histology (22% vs. 3%, P = 0.055), grade 3 disease (42% vs. 16%, P < 0.001), and stage IC disease (21% vs. 3%, P = 0.001) when compared to patients < 45 years old. Evaluation of endometrioid tumors only revealed a similar pattern of deeper myometrial invasion and higher tumor grade as age increased. CONCLUSIONS: Younger patients with endometrial cancer are generally more obese, with lower grade, lower stage disease, and with more favorable histologic cell types. Despite this, approximately a quarter have stage II-IV disease and 9% have positive lymph nodes. The older patients represent a dramatically different subset of patients. They are more likely to have aggressive papillary serous histology, higher grade tumors, and advanced stage disease. Age should be a consideration in appropriate referrals to gynecologic oncologists.

Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid.

The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), are currently being considered as prospective drug candidates for treatment of type 2 diabetes. Interest in these gut hormones was initially spurred by their potent insulinotropic activities, but a number of other antihyperglycaemic actions are now established. One of the foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV). Here, we compare the DPP IV resistance and biological properties of Abu8/Abu2 (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered to impart DPP IV resistance. Whereas (Abu8)GLP-1 was completely stable to human plasma (half-life >12 h), GLP-1, GIP, and (Abu2)GIP were rapidly degraded (half-lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly (Abu8)GLP-1 elicited significant adenylate cyclase and insulinotropic activity, while (Abu2)GIP was less effective. Similarly, in obese diabetic (ob/ob) mice, GIP, GLP-1, and (Abu8)GLP-1 displayed substantial glucose-lowering and insulin-releasing activities, whereas (Abu2)GIP was only weakly active. These studies illustrate divergent effects of penultimate amino acid Ala8/Ala2 substitution with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu8)GLP-1 represents a potential candidate for future therapeutic development.

N-terminal His(7)-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity.

Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC(50) values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC(50) 0.37 nM). Similarly, both analogues stimulated cAMP production with EC(50) values of 16.3 and 27 nM respectively compared with GLP-1 (EC(50) 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P<0.05 to P<0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes.

Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39).

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLP-1's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His(7) and Ala(8), can greatly improve resistance to this enzyme. Little research has assessed what effect Glu(9)-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu(9) of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue, (Lys(9))GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1(9-36)amide. We investigated the in vivo antagonistic actions of (Lys(9))GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor.

Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs. cisplatin and paclitaxel (GOG 158) and an update on GOG0 182-ICON5.

Mature results from GOG158 have clearly established carboplatin and paclitaxel as an effective and well tolerated standard regimen, providing a basis for the reference arm in GOG0182-ICON5, an ongoing multiarmed phase III trial of the Gynecologic Cancer InterGroup (GCIG) evaluating the incorporation of newer cytotoxic agents. Results from GOG158 will be reviewed, including an analysis of second-look surgical outcomes, followed by an update on the current status of GOG0182-ICON5.

Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel versus cisplatin and paclitaxel (GOG158) and an update on GOG0182-ICON5.

Mature results from GOG158 have clearly established carboplatin and paclitaxel as an effective and well-tolerated standard regimen, providing a basis for the reference arm in GOG0182-ICON5, an ongoing multiarmed phase III trial of the Gynecologic Cancer InterGroup (GCIG) evaluating the incorporation of newer cytotoxic agents. Results from GOG158 will be reviewed, including an analysis of second-look surgical outcomes, followed by an update on the current status of GOG0182-ICON5.

Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo.

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

The effect of body mass index on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of body mass index (BMI) on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington, between 1 January 1990 and 1 January 2000 were eligible; 439 patients were identified and 43 were excluded due to incomplete medical records; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 27 months (range, 1 to 120 mo). RESULTS: Mean BMI was 34 (range, 15 to 69). BMI was <30 in 40.7% of patients, 30 to 40 in 32.3%, and >40 in 27.0%. Clinically, patients with a BMI of >40 were more likely to have hypertension, diabetes, and pulmonary disease. Those patients with a BMI of >40 had statistically longer operating times (209 vs. 159 min) and more blood loss (604 vs. 324 ml) than patients with a BMI of <30. However, there was no difference between the three groups in number of lymph nodes removed, units of blood transfused, length of hospital stay, number of intensive care unit (ICU) days, or intraoperative complications. Postoperatively, patients with a BMI of >40 were more likely to have a wound separation than thinner patients. Pathologically, patients with a BMI of >40 were more likely to have endometrioid histology, lower stage disease, and lower grade tumors than women with a BMI of <30. However, 11.3% of patients with lymph node sampling and a BMI of >40 had positive lymph nodes and 23% were stage II or higher. Forty-two patients (10.6%) recurred. There were no postoperative deaths, and there was no difference in survival between the three groups. CONCLUSIONS: Patients with a BMI of >40 frequently have favorable stage I endometrial cancers. However, approximately a quarter of these patients have evidence of cervical or extrauterine disease. This study confirms that surgical staging can be performed adequately and safely in morbidly obese patients with no difference in length of hospital stay, number of ICU days, intraoperative or postoperative complications.

Sealing ability of Dyract, Geristore, IRM, and super-EBA as root-end filling materials.

The purpose of this study was to evaluate the apical sealing ability of two compomers (Dyract and Geristore), IRM, and Super-EBA. Forty single canal roots from human teeth were instrumented until a size 40 file extended 1 mm beyond the apex. One millimeter of root apex was removed and a preparation 3-mm deep was prepared. Roots were divided into 4 groups of 10 roots each and filled with IRM, Super-EBA, Dyract, or Geristore. Canals were not obturated to ensure that any leakage was due to the apical filling material alone. Each root was then affixed to a fluid filtration device and subjected to a pressure of 14 cm of H2O, which has been determined to be the normal pulpal tissue pressure. The integrity of the seal was evaluated for 5 min at 1, 7, 30, and 180 days. Data were analyzed at each time point using one-way analysis of variance on ranks. The results of this study suggest that the new compomers Dyract and Geristore are equal or superior to IRM and equivalent to Super-EBA in their ability to reduce apical leakage when used as retrofilling materials.

Identification of the region of non-Abeta component (NAC) of Alzheimer's disease amyloid responsible for its aggregation and toxicity.

The non-beta-amyloid (Abeta) component of Alzheimer's disease amyloid (NAC) and its precursor alpha-synuclein have been linked to amyloidogenesis in several neurodegenerative diseases. NAC and alpha-synuclein both form beta-sheet structures upon ageing, aggregate to form fibrils, and are neurotoxic. We recently established that a peptide comprising residues 3-18 of NAC retains these properties. To pinpoint the exact region responsible we have carried out assays of toxicity and physicochemical properties on smaller fragments of NAC. Toxicity was measured by the ability of fresh and aged peptides to inhibit the reduction of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) by rat pheochromocytoma PC12 cells and human neuroblastoma SHSY-5Y cells. On immediate dissolution, or after ageing, the fragments NAC(8-18) and NAC(8-16) are toxic, whereas NAC(12-18), NAC(9-16) and NAC(8-15) are not. Circular dichroism indicates that none of the peptides displays beta-sheet structure; rather all remain random coil throughout 24 h. However, in acetonitrile, an organic solvent known to induce beta sheet, fragments NAC(8-18) and NAC(8-16) both form beta-sheet structure. Only NAC(8-18) aggregates, as indicated by concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. These findings indicate that residues 8-16 of NAC, equivalent to residues 68-76 in alpha-synuclein, comprise the region crucial for toxicity.

Evaluation of chemoresistance markers in women with epithelial ovarian carcinoma.

OBJECTIVE: Preliminary studies have suggested that lung resistance protein (LRP), multidrug resistance protein (MRP), and p27 may be useful markers of chemoresistance. Our goal was to evaluate the expression of LRP, MRP, and p27 in normal ovaries and chemosensitive and chemoresistant ovarian carcinomas. METHODS: Fourteen women with normal ovaries and fifty women with epithelial ovarian carcinoma who underwent cytoreductive surgery from 1996 through 1998 had specimens stained with immunocytochemistry for LRP, MRP, and p27. All women received paclitaxel/platinum-based chemotherapy. Twenty-nine women had a disease-free survival (DFS) of at least 12 months after completion of chemotherapy (sensitive) and 21 women had persistent disease during treatment (resistant). RESULTS: Evaluation of LRP expression revealed significant differences between the normal ovaries and cancers in both the epithelial (57% vs 90%, P = 0.03) and stromal (86% vs 32%, P = 0.001) components. Evaluation of MRP expression revealed significant differences between normal ovaries and cancers in the epithelial component (7% vs 66%, P = 0.001) but not in the stromal component (14% vs 4%, P = 0.1). Evaluation of p27 revealed significant reductions in expression in cancers compared with normal ovaries for both the epithelial (90% vs 55%, P = 0.02) and stromal (88% vs 5%, P = 0.001) components. Comparison between the chemosensitive and chemoresistant groups revealed no significant differences in expression of LRP and MRP, in either the epithelial or stromal component, but significantly lower levels of p27 were expressed in the epithelial component of the chemoresistant group (P = 0.01). CONCLUSIONS: The expression of LRP, MRP, and p27 is significantly different in ovarian cancers compared with normal ovaries. Low levels of p27 expression are associated with chemoresistance; however, LRP and MRP expression are not prognostic for chemosensitivity.

Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis.

OBJECTIVE: BRCA-1 and BRCA-2 germline mutations increase the risk of ovarian and breast cancer. Primary cancer of the fallopian tube is rare; however, recent evidence suggests that patients harboring a germline mutation conferring an increased risk of ovarian cancer may be at risk for fallopian tube cancer as well. We discuss the finding of occult fallopian tube cancer diagnosed at surgical prophylaxis in women harboring BRCA-1 mutations. METHODS/RESULTS: Two patients undergoing surgical prophylaxis to address an increase in ovarian cancer risk were discovered to harbor occult primary fallopian tube carcinoma on final pathology review. Mutational analysis confirmed the presence of a deleterious mutation in BRCA-1 in both patients. CONCLUSION: Currently, consensus opinions regarding ovarian cancer surgical prophylaxis in gene mutation carriers do not include hysterectomy as part of the preventative procedure. This report as well as a growing number of cases of fallopian tube cancer reported in known BRCA-1 and BRCA-2 mutation carriers has important implications for recommendations regarding surgical prophylaxis in these women.

Phase I trial of escalating doses of paclitaxel combined with fixed doses of cisplatin and doxorubicin in advanced endometrial cancer and other gynecologic malignancies: a Gynecologic Oncology Group study.

PURPOSE: The primary objective of this phase I trial was to determine the feasibility of administering a combination of paclitaxel, cisplatin, and doxorubicin with or without granulocyte colony-stimulating factor (G-CSF) in patients with advanced endometrial and other gynecologic cancers. PATIENTS AND METHODS: Patients were chemotherapy-naive. Doxorubicin was administered as a brief infusion, paclitaxel for 3 hours, and cisplatin for 60 minutes. Treatments were repeated every 3 weeks. For most dose levels, the cisplatin and doxorubicin were fixed at 60 mg/m(2) and 45 mg/m(2), whereas the paclitaxel was escalated in successive cohorts from 90 to 250 mg/m(2). Patients who had received previous radiotherapy to the whole pelvis were escalated separately from those who had not. RESULTS: Eighty patients received 320 cycles of therapy. When G-CSF was not used, myelosuppression prevented escalation beyond the starting dose for patients with or without previous pelvic radiotherapy. When G-CSF was added, neurotoxicity became dose-limiting for both groups. Ten patients were removed from the study for asymptomatic declines in ejection fraction, but no symptomatic congestive heart failure was observed. Major antitumor responses occurred in 46% of patients (six of 13) with measurable endometrial carcinoma and 50% of patients (eight of 16) with measurable cervical carcinoma. CONCLUSION: The combination of paclitaxel, doxorubicin, and cisplatin at relevant single-agent doses is active and feasible with the addition of G-CSF. A regimen of cisplatin 60 mg/m(2), doxorubicin 45 mg/m(2), and paclitaxel 160 mg/m(2) with G-CSF support is recommended for further testing.

Occupational Exposure in Nuclear Medicine and PET.

Purpose: With the increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for scanning in oncology in our center, a radiation dose survey was performed to determine the impact on staff exposure. Conventional nuclear medicine procedures such as gallium scan, bone scans, and sestamibi cardiac scans are used for comparative purposes.Procedure: Patients were measured using a hand-held radiation monitor (Victoreen 450-P) at various distances and times that replicate typical patient contact scenarios in the Diagnostic Imaging Department.Results: We present our findings from the survey and the implications these have on staff radiation exposure. The data suggest that emerging oncologic techniques such as PET, high dose gallium-67, and high dose Tl-201 do not represent a significantly greater occupational radiation hazard than conventional nuclear medicine procedures.

Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer.

OBJECTIVE: Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis. Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent pattern of deregulation has been characterized. Vascular endothelial growth factor (VEGF) has emerged as an important regulator of tumor neovascularization. Recent work has shown that SPARC modulates the mitogenic activity of VEGF in normal endothelium. While its role in malignant transformation remains elusive, SPARC may contribute to tumor propagation and invasion. This study examines the immunoreactivity of SPARC and VEGF associated with neoplastic transformation of the ovary. METHODS: Immunostaining for VEGF and SPARC protein was performed on 62 archival specimens. RESULTS: Fourteen normal ovaries and 48 ovarian carcinomas were evaluated. SPARC was detected in the stroma of 63% of ovarian carcinomas. In contrast, SPARC was observed in the stroma of only 29% of normal ovaries (P = 0.02). Furthermore, SPARC was limited in normal ovaries to premenopausal patients, juxtaposed either with vesiculated follicles or within the corpus luteum. VEGF was observed in 42% of ovarian carcinomas with immunoreactivity confined to tumor cells. The level of VEGF immunoreactivity was significantly higher in ovarian carcinoma compared to normal ovary epithelium (42 vs 7%, P = 0.02). CONCLUSIONS: Immunoreactivity of SPARC and VEGF is heightened in association with ovarian carcinoma, with a distinct distribution of SPARC in the stroma of neoplastic ovaries and VEGF within tumor cells. No obvious pattern of coincident SPARC and VEGF immunoreactivity was detected. These results indicate the possibility of an aberration in the interaction that has been described in normal endothelium between SPARC and VEGF in association with malignant transformation.

Phase I study of paclitaxel, carboplatin, and increasing days of prolonged oral etoposide in ovarian, peritoneal, and tubal carcinoma: a gynecologic oncology group study.

PURPOSE: Given the activity of prolonged oral etoposide in platinum and paclitaxel-resistant ovarian carcinoma, a phase I trial was conducted that combined increasing days of oral etoposide therapy with paclitaxel and carboplatin in chemotherapy-naive patients with ovarian peritoneal and tubal carcinoma to establish a maximum-tolerated dose (MTD) of this combination. PATIENTS AND METHODS: Paclitaxel at 175 mg/m(2) given over 3 hours and carboplatin at an area under the curve of 5 were administered on day 1 followed by oral etoposide 50 mg/m(2)/d beginning on day 2. The number of days of etoposide therapy was escalated on the basis of toxicity. Toxicity end points included neutropenic sepsis, grade 4 thrombocytopenia, or grade 3 neutropenia or thrombocytopenia during etoposide administration. Cycles were repeated every 21 days for a maximum of six courses. Due to hematologic toxicity, the duration of the paclitaxel infusion was decreased to 1 hour for a second stage of accrual. RESULTS: Of 52 patients studied, 29 were in the first stage of accrual. Dose-limiting toxicity occurred with 8 days of oral etoposide, making the MTD six days of therapy. Twenty-three patients were entered into the second stage of accrual. Dose-limiting toxicity occurred at 12 days of oral etoposide, making the MTD 10 days of therapy. Three patients developed acute myeloid leukemia 16, 27, and 35 months after receiving a cumulative dose of 200 mg/m(2), 1,200 mg/m(2), and 2,400 mg/m(2), respectively. CONCLUSION: One-hour paclitaxel, carboplatin, and oral etoposide at 50 mg/m(2)/d for 10 days is tolerable without supportive therapy. The leukemogenic potential is cause for concern and precludes its use in chemotherapy-naive ovarian carcinoma.