Secondary Treatment Group Research Articles

Optimal sequencing of the first- and second-line target therapies in metastatic renal cell carcinoma: based on nationally representative data analysis from the Korean National Health Insurance System

BackgroundThe authors intend to compare the effects of each targeted therapy (TT) in the treatment of patients with metastatic renal cell carcinoma (mRCC) using big data based on the Korean National Health Insurance System (NHIS) and determine the optimal treatment sequence.MethodsData on the medical use of patients with kidney cancer were obtained from the NHIS database from January 1, 2002, to December 31, 2020. Patient variables included age, sex, income level, place of residence, prescribing department, and duration from diagnosis to the prescription date. The primary outcome was overall survival (OS) for each drug and sequencing. We performed propensity score matching (PSM) according to age, sex, and Charlson Comorbidity Index based on the primary TTs.ResultsAfter 1:1 PSM, the sunitinib (SUN) (n = 1,214) and pazopanib (PAZ) (n = 1,214) groups showed a well-matched distribution across the entire cohort. In the primary treatment group, PAZ had lower OS than SUN (HR, 1.167; p = 0.0015). In the secondary treatment group, axitinib (AXI) had more favorable OS than cabozantinib (CAB) (HR, 0.735; p = 0.0118), and everolimus had more adverse outcomes than CAB (HR, 1.544; p < 0.0001). In the first to second TT sequencing, SUN–AXI had the highest OS; however, there was no statistically significant difference when compared with PAZ–AXI, which was the second highest (HR, 0.876; p = 0.3312). The 5-year survival rate was calculated in the following order: SUN–AXI (51.44%), PAZ–AXI (47.12%), SUN–CAB (43.59%), and PAZ–CAB (34.28%). When the four sequencing methods were compared, only SUN–AXI versus PAZ–CAB (p = 0.003) and PAZ–AXI versus PAZ–CAB (p = 0.017) were statistically significant.ConclusionsIn a population-based RWD analysis of Korean patients with mRCC, SUN-AXI sequencing was shown to be the most effective among the first to second TT sequencing methods in treatment, with a relative survival advantage over other sequencing combinations. To further support the results of this study, risk-stratified analysis is needed.

Iron chelation effects on lipid peroxidation, inflammation and ventricular performance in a rat model of isoproterenol induced acute myocardial stress.

Acute cardiac pathologies represent one of the leading causes of death, while iron metabolism is recognized to be implicated in reactive oxygen species production, lipid peroxidation, and inflammation. The aim of the present study was to assess iron chelation effects in isoproterenol (ISO) induced acute cardiac stress. We divided male Wistar rats into preventive and secondary treatment groups, with the active arm consisting in deferiprone (DFP), a lipid permeable chelator. Mortality of ISO was 10-18.18% in both preventive and secondary groups. We analyzed serum and myocardial tissue parameters of inflammation, iron dynamics, and lipid peroxidation, accompanied by ultramicroscopy, histological, and ultrasound-derived parameters of left ventricular function. Results reveal that ISO-mediated lipid peroxidation and inflammation are alleviated by administration of DFP, with negligible effect on systemic ferroregulation dynamics and global ventricular function (as assessed by ultrasound). DFP administration after cardiovascular stress is associated with a decrease in lipid peroxidation and inflammation, without an improvement in gross left ventricular parameters.

Evaluation of statin discontinuation stratified by primary versus secondary prevention following bariatric surgery: a retrospective cohort study.

Bariatric surgery leads to an improvement in hyperlipidemia and a subsequent decline in the use of hyperlipidemia-related medications, including statins. In patients with a history of atherosclerotic cardiovascular disease (ASCVD), it is recommended to continue statins; however, it is unknown whether there is a differential risk for statin discontinuation in patients with and without a history of ASCVD. To estimate the rates and factors associated with statin discontinuation following bariatric surgery. Large U.S. administrative claims database of privately insured beneficiaries, January 2005 through December2017. We identified patients aged ≥19 years who were statin users at the time of bariatric surgery. Patients were stratified into primary prevention and secondary prevention (patients with a history of ASCVD) groups. Time to statin discontinuation was defined as the first 90-day gap after exhausting the last day's supply of the last statin prescription. Factors associated with statin discontinuation were assessed using the Cox proportional hazards regression model. We identified 19,332 statin users at the time of bariatric surgery, of whom 84% (16,221) used statins for primary prevention. At 6 months, 62% and 53% of patients in the primary and the secondary prevention treatment groups, respectively, discontinued statin use. Patients in the primary prevention treatment group were 18% more likely to discontinue statin therapy compared with the patients in the secondary prevention treatment group (hazard ratio, 1.18; 95% confidence interval, 1.13-1.24) according to a multivariable analysis. Our findings suggest that the rate of discontinuation of statin therapy after bariatric surgery was more pronounced in the primary versus secondary prevention treatment group.

Is conventional management of primary spontaneous pneumothorax appropriate?

This study aimed to evaluate the recurrence rate after primary and secondary conservative treatments and to clarify the validity of current primary spontaneous pneumothorax management by comparing secondary conservative treatment and surgical outcomes. Data from 166 patients with primary spontaneous pneumothorax treated at a single site between September 2015 and March 2019 were retrospectively evaluated. Patient characteristics of those who received primary conservative therapy (n = 166) and secondary conservative therapy (n = 28) were summarized. The outcomes from patients who experienced recurrence (n = 64) were compared based on those who underwent surgery (n = 24) and those who underwent secondary conservative therapy (n = 28). The post-treatment day 60 recurrence rate was 27.1 and 49.5% cases in the primary and secondary treatment groups, respectively, which was significantly higher after secondary treatment than after primary treatment with conservative therapy (p = 0.032). The post-treatment one-year recurrence rate was 13.5 and 57.9% in patients who underwent surgery and secondary conservative treatment, respectively; secondary conservative treatment resulted in a significantly higher recurrence rate than surgery (p < 0.001). There is evidence for guidelines that recommend surgery for recurrent primary spontaneous pneumothorax after primary conservative therapy based on its lower and more delayed post-treatment recurrence rate than secondary treatment with conservative therapy.

Combining intraoperative ultrasound-guided irreversible electroporation with chemotherapy for treating locally advanced pancreatic cancer: a clinical report of 64 cases

Objective: To examine the safety and clinical efficacy of ultrasound-guided irreversible electroporation (IRE) using the open surgery approach, after induction chemotherapy, in the treatment of locally advanced pancreatic cancer (LAPC) . Methods: The data of 64 LAPC patients who underwent ultrasound-guided IRE using the open surgery approach after induction chemotherapy at Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center from August 2015 to March 2019 were retrospectively analyzed. The study comprised of 30 males and 34 females, with median age of 58.5 years old (range: 34 to 87 years old) , were included in this study.The tumor was located in the pancreatic head and body/tail in 30 and 34 patients, respectively.The largest recorded tumor size was 6.1 cm (≤4.0 cm: n=35; >4.0 cm: n=29) .To create an electric field around the tumor, Two to six probes were parallelly inserted into each patient's tumor, based on the size of the tumor, at a distance of 2 cm apart through the transverse mesocolon in a caudal-to-cranial direction.According to the numerical sequence of patients undergoing ultrasound-guided IRE, the first 15 cases and following 49 patients were categorized as the primary and secondary treatment group, respectively.T text or χ(2) test was analyzed to the data between two groups.The study endpoints were overall survival (OS) and progression free survival (PFS) , which were investigated using Kaplan-Meier method, and their differences were compared using log-rank test. Results: The overall length of hospital stay was (8.9±2.7) days (range: 5 to 20 days) . Four patients were lost to follow-up.The study follow-up rate was 93.8%, with a median follow-up time of 29.3 months (range: 13.5 to 55.7 months) .The median OS and PFS of the entire cohort was 24.6 months (95% CI: 22.0 to 27.3 months) and 12.0 months (95%CI: 8.8 to 15.2 months) , respectively.One month after IRE, abdominal pain was significantly relieved in 95.3% of the patients (t=-28.55, P<0.01) .The rate of complications in the entire cohort was 20.3% and all were classified as grade B.Of them, pancreatic fistula, incisional infection, and upper gastrointestinal hemorrhage were observed in 7, 4, and 2 cases, respectively.The rate of complications for patients in the primary and secondary treatment groups were significantly different (10/15 vs. 6.1%) , respectively (χ(2)=26.01, P<0.01) .Further, two deaths were observed after IRE in the primary treatment group, while none was observed in the secondary treatment group. Conclusions: Ultrasound-guided IRE using the open surgery approach after induction chemotherapy is found to be safe and effective in treating patients with LAPC.However, these findings should be validated in prospective randomized trials before wide clinical application.

P973Intravascular lithotripsy for lesion preparation in calcified coronary lesions: a prospective, observational, two-center registry

Abstract Background Intravascular coronary lithotripsy (IVL) is a novel alternative treatment for heavily calcified lesions. This study sought to determine the strategy success and safety of IVL on calcified lesions in an all-comers cohort of patients. Methods Patients with moderate and severely calcified coronary lesions were screened in two centers in Spain and Germany starting April 2018. Until February 2019, 61 patients with 67 lesions were eligible for IVL. Patients were assigned to the following groups: A) Primary IVL therapy for patients with circumferential calcified de-novo coronary lesions (n=32), B) Secondary IVL therapy for patients with moderate or severe calcified coronary lesions in which conventional non-compliant balloon dilatation failed (n=18) and C) Tertiary IVL therapy in patients with in-stent stenosis due to stent underexpansion after previous stenting (n=17). Primary endpoint was strategy success and safety outcome. Strategy success was defined as successful stent delivery and expansion with attainment of &lt;20% in-stent residual stenosis of the target lesion. Safety outcome were procedural complication, defined as coronary dissection, slow or no-reflow phenomenon, new coronary thrombus formation during PCI, abrupt vessel closure and device failure (inability to place the balloon, malfunction, or burst) and in hospital MACE. Results 61 patients with 67 calcified lesions were treated with IVL. Mean diameter of calcified stenosis on quantitative coronary angiography was 72.02±13.8% at baseline and decreased to 17.7±15.84% (p-value: &lt;0.01) after IVL with an acute gain of 1.9±0.63 mm. Mean minimal lumen diameter was 1.0±0.5 mm at baseline and increased after IVL to 2.9±0.6 mm. The overall average of applied pulses was 63±22. The primary endpoint of strategy success was reached overall in 85.2% of patients. 4 type b dissections (3 in group A, 1 in group B) were observed without further sequelae. There were no in-hospital MACE. In one patient (1.6%) non-ischemia driven target lesion failure was observed in routine follow up coronary angiography and was in need for revascularization. According to the subgroups, strategy success in primary IVL treatment (group A) and secondary IVL treatment (group B) was reached in 81.3% and 83.3% of cases, respectively. In tertiary IVL therapy (group C), the primary study endpoint was reached in 64.7% of cases. Device delivery and IVL treatment of target lesion could be performed in all lesions without vessel complications. 7 IVL balloons ruptured during treatment without any sequelae. Rupture was observed in most cases after repositioning of the balloon within the calcified lesion. Conclusions IVL provides a valid strategy for lesion preparation in severely calcified coronary lesions, with high success rate, and low procedural complication and MACE rates. Longitudinal studies will confirm if these favourable initial results of IVL-supported PCI are followed by good long-term results.

Pengaruh Monoklonal Antibodi Bovine Zona Pelusida 3 (bZP3) terhadap Diameter dan Atresia Folikel Ovarium Mencit (Mus musculus)

Objectives: To identify the effect of monoclonal antibody bZP3 at ovarian follicles that undergo atresia and diameter of various ovarian follicles.Materials and Methods: This is a true experimental research with post only control group design. Samples were 36 female mices (Mus musculus) which is divided into 6 groups, there are 3 control groups (group 1, 2, and 3) injected by Phospatase Buffer Saline (PBS) 50µl and 3 treatment groups (group 4, 5, and 6) injected by Mab bZP3 50µl. Group 1 and 4 terminated at 5th day, group 2 and 5 terminated at 10th day, and group 3 and 6 terminated at 20th day. Evaluation of atretic ovarian follicles and diameter of ovarian follicles performed by hematoxylin eosin (HE) and the data processed by parametric statistic.Results: There are no significant in different among groups in the aspect of atretic follicles and diameter of folicles (p&gt;0.05), but descriptively, number of follicles undergo atresia of the follicle primary, secondary, and tertiary treatment group was higher than the control group, except on the 20th day of observation time.Conclusion: administration of Mab bZP3 had no effect to amount of atretic follicles and diameter of folicles during observation time.

Gamma Knife Radiosurgery for Petroclival Meningioma: Long-Term Outcome and Failure Pattern

Total removal of petroclival meningioma is difficult, and aggressive extirpation is often associated with significant surgical morbidity and mortality. The aim of this study was to evaluate the long-term outcome and failure pattern of treatment with Gamma Knife radiosurgery (GKRS) in patients with petroclival meningiomas. Eighty-nine consecutive patients with petroclival meningiomas underwent GKRS between 1998 and 2013. Fifty-eight patients received GKRS as a primary treatment and 31 patients underwent GKRS as a secondary treatment after microsurgery. The mean tumor volume was 6.7 cm³ (range, 0.5-46.3 cm³) and the mean marginal dose was 13.2 Gy (range, 8-17 Gy). At the last radiological follow-up, tumor volume was decreased in 50 patients (56.2%), stationary in 34 patients (38.2%), and increased in 5 patients (5.6%). The actuarial progression-free survival after GKRS was 94.7% at 5 years and 88.9% at 10 years. Favorable cranial nerve outcomes were found in 81 patients (91%). A regrowth pattern was present in all 4 patients of the primary treatment group, whereas cyst formation (3 patients) and regrowth (1 patient) were observed in the secondary treatment group. GKRS is an effective and reasonable option as a primary or secondary treatment for petroclival meningioma. Further studies of failure patterns after GKRS for petroclival meningioma are mandatory.

Modulation of the innate immune-related genes expression in H9N2 avian influenza virus-infected chicken macrophage-like cells (HD11) in response to Escherichia coli LPS stimulation

Macrophages play important roles in mediating virus-induced innate immune responses and are thought to be involved in the pathogenesis of bacterial superinfections. The innate immune response initiated by both low pathogenicity AIV and bacterial superinfection in their avian host is not fully understood. We therefore determine the transcripts of innate immune-related genes following avian H9N2 AIV virus infection and E. coli LPS co-stimulation of avian macrophage-like cell line HD11 cells. More pronounced expression of pro-inflammatory cytokines (IL-6 and IL-1β) as well as the inflammatory chemokines (CXCLi1 and CXCLi2) was observed in virus infected plus LPS treated HD11 cells compared to H9N2 virus solely infected control. For two superinfection groups, the levels of genes examined in a prior H9N2 virus infection before secondary LPS treatment group were significantly higher as compared with simultaneous virus infection plus LPS stimulation group. Interestingly, similar high levels of IL-6 gene were observed between LPS sole stimulation group and two superinfection groups. Moreover, IL-10 and TGF-β3 mRNA levels in both superinfection groups were moderately upregulated compared to sole LPS stimulation group or virus alone infection group. Although TLR4 and MDA5 levels in virus alone infection group were significantly lower compared to that in both superinfection groups, TLR4 upregulation respond more rapid to virus sole infection compared to LPS plus virus superinfection. Collectively, innate immune-related genes respond more pronounced in LPS stimulation plus H9N2 virus infection HD11 cells compared to sole virus infection or LPS alone stimulation control cells.

Subthreshold diode-laser micropulse photocoagulation as a primary and secondary line of treatment in management of diabetic macular edema.

BackgroundThe purpose of this study was to evaluate subthreshold diode-laser micropulse (SDM) photocoagulation as a primary and secondary line of treatment for clinically significant diabetic macular edema (CSDME).MethodsIn this prospective nonrandomized case series, 220 cases of nonischemic CSDME were managed primarily and secondarily by SDM photocoagulation on a 15% duty cycle with a mean power of 828 mW and a spot size of 75–125 μm. SDM treatment was repeated at 3–4-month intervals if residual leakage was observed. Additional intravitreal pharmacologic therapy was used according to the response. Follow-up varied from 12 to 19 (mean 14±2.8) months. Novel software designed by the authors was used to record the subvisible threshold laser applications and their parameters on the fundus image of the eye. Evaluation of the results of treatment was done using fluorescein angiography and optical coherence tomography (OCT). Primary outcome measures included changes in visual acuity and foveal thickness at OCT. Secondary outcome measures included visual loss of one or more Snellen lines and laser scars detectable on fundus biomicroscopy or fluorescein angiography.ResultsIn the primary treatment group, there was significant improvement or stabilization of visual acuity after the first 3–4 months, which was stable thereafter. Visual acuity was stable in the secondary treatment group. A corresponding reduction of macular thickness on OCT was noted during the follow-up period in both groups. Additional therapy included repeat SDM photocoagulation, intravitreal injection of triamcinolone, and pars plana vitrectomy. Laser marks seen as changes in retinal pigment epithelium on fundus biomicroscopy and fluorescein angiography were noted in 3.3% and 5.7% of cases. Our novel software could accurately record the location of all SDM-invisible applications.ConclusionMicropulse laser is an effective minimal intensity therapy that offers the clear advantage of minimizing or avoiding laser-induced visible retinal burn/scarring while reducing the foveal thickness in the management of selected cases of CSDME. Future prospective studies should include the use of SDM photocoagulation as a combined minimally invasive therapy to consolidate the prompt but temporary effects of anti-vascular endothelial growth factor or anti-inflammatory agents. Virtual localization of SDM-invisible applications using our proprietary software could be used to guide further retreatments.

Clinical characteristics and effect of secondary individualized therapy in chronic hepatitis B patients infected with the rtA181 mutation hepatitis B virus

To investigate chronic hepatitis B (CHB) patients infected with the antiviral-resistant rtA181 mutation hepatitis B virus (HBV) who have been unresponsive to general therapy to determine the effects of individualized therapy. Fifty-four patients with confirmed rtA181 mutation and who experienced virological breakthrough during nucleus(t)ide analogue (NUC) treatment were enrolled in this prospective cohort study. Their serum levels of HBV DNA, hepatitis B surface antigen (HBsAg), and alanine transaminase (ALT) were tested. Each patient was genotyped by pyrosequencing for 10 mutation sites in the HBV P gene that have been previously correlated to NUC efficacy. Each patient's antiviral therapy and response history was analyzed in regard to their particular mutation pattern. The serological index was determined for carriers of the rtA181T/V mutation. The secondary individualized treatment included adding/switching to entecavir (ETV; group A) or adding telbivudine (LdT; group B) upon confirmation of drug resistance. Effect of individualized treatment was analyzed by T test and Mann-Whitney U test for continuous variables with normal or skewed distributions, respectively. Categorical variables were analyzed by the Chi-squared ( x² ) or Fisher's exact tests. The rtA181T mutation was found in 64.8% (35/54) of patients with rtA181 mutation HBV. The most frequent previously administered medications were adefovir dipivoxil (ADV) and lamivudine (LAM). Multi-site rtA181 mutations occurred more frequently in the patients with multi-NUCs history (57.6%) than in those with single NUCs history (28.6%) (x²=4.342, P less than 0.05). Serum HBV DNA level at virological breakthrough was lower than that at baseline of the first antiviral treatment (5.66+/-1.01 vs. 6.75+/-0.81 log10 copies/ml; t=-4.210, P less than 0.01). The serum HBsAg level was higher in carriers of the rtA181T mutation than in carriers of the rtA181V mutation (3.80+/-0.45 vs. 3.46+/-0.60 log10 IU/ml; t=2.109, P less than 0.05). In patients with serum HBV DNA more than or equal to 6 log10 copies/ml at viral breakthrough, 100% (8/8) of patients in the secondary treatment group A and 75% (3/4) patients in the secondary treatment group B exhibited virological response at week 24 after intervention. Undetectable HBV DNA was achieved in three patients of group A and one patient of group B. In patients with serum HBV DNA less than 6 log10 copies/ml at viral breakthrough, 100% (14/14) of patients in group A and 71.4% (5/7) of patients in group B exhibited biological response at week 24 after intervention. The serum HBV DNA level decreased to undetectable levels in 12 patients of group A and four patients of group B. The rtA181 mutation pattern correlates with previous antiviral therapy response. In addition, multi-site rtA181 mutations occur more frequently in patients with a history of multi-NUCs therapy. Adding or switching rtA181 carriers to ETV produces a more robust virological suppression than adding LdT.

The efficacy of octreotide LAR in acromegalic patients as primary or secondary therapy

The objective of this study was to investigate the efficacy of octreotide therapy in acromegalic patients as primary or secondary therapy. Ten acromegalic patients diagnosed at the Endocrinology Clinic in Sarajevo (seven females and three males, mean age 55.2 ± 7.2 years, age range 40-65 years, five patients with microadenoma and five patients with macroadenoma) were treated with octreotide. Among them, 60% of patients were operated on and the majority of the procedures were performed transnasaly (90%). That group of patients had recidivism of disease (pituitary adenoma and acromegaly). The concentration of human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1) was evaluated at 0, 6 and 12 months, while magnetic resonance imaging (MRI) was taken before the treatment and 12 months after. Eight patients received octreotide 30 mg/28 days, one patient received a dose of 20 mg and the other received 60 mg/28 days. Before treatment growth hormone (GH) levels were 50.87 ± 10.56 ng/ml (range: 26-64.9), IGF-1 were 776.66 ± 118.40 ng/ml (range: 526-934). Four patients (40%) were treated with primary octreotide treatment and six patients (60%) with secondary somatostatin analog treatment. At the beginning of therapy, there were no differences in terms of age, HGH levels and IGF-1 levels between primary and secondary treatment groups (p > 0.05). The difference between groups was only in regard to the size of tumors (p = 0.01). After 6 and 12 months the GH levels decreased to 1.61 ± 0.86 ng/ml (range: 0.7-2.65) and 1.85 ± 2.40 ng/ml (range: 0.0-8.3), respectively, while the IGF-1 became 305.90 ± 43.19 ng/ml after 6 months of treatment (range: 240-376) and 256.99 ± 71.43 ng/ml after 12 months of octreotide treatment (range: 126-325), respectively. The pituitary adenomas size prior to treatment was 9.57 mm, while after 12 months of treatment, the size decreased to 8.0 mm. After therapy, a GH decrease to less than 2.5 ng/ml was achieved in 90% of cases; tumor size decrease was achieved in 60% while normalization of IGF-1 was achieved in 100% of the patients, respectively. All differences about HGH and IGF-1 in each group were statistically significant (p < 0.05). In the group of acromegalic patients treated with octreotide LAR as primary therapy, the difference was more significant for GH and IGF-1 than for adenomas size. Octreotide treatment of acromegaly not only decreases GH and IGF-1 concentrations, but also appears to diminish the size of the tumor in about 60% of cases. The somatostatin analogs are more efficient in the primary treatment of acromegalic patients, due to the fact that primary therapy is as effective as secondary therapy but primary therapy has small advantages when compared with secondary octreotide therapy because no surgical treatment is required before.

Clinical relevance of extent of extreme drug resistance in epithelial ovarian carcinoma

Objective The objective of this study was to evaluate the clinical significance of the extent of extreme drug resistance (EDR) in in vitro drug resistance assays in advanced epithelial ovarian, fallopian, and primary peritoneal cancers. Methods A retrospective study was conducted using the database for in vitro drug resistance assay (EDR Assay®, Oncotech, Inc.) results for advanced stage ovarian cancer samples obtained at primary surgery between 1995 and 2009. In vitro drug resistance assay results were evaluated for thirteen drugs according to the following two groups: platinum and taxane (primary treatment group) vs remaining agents (secondary treatment group). Dual-resistance was then defined as at least one EDR in the primary and secondary treatment groups. Chemotherapy response and survival outcome were correlated with assay results. Results There were 253 cases identified. Dual-resistance ( n = 53, 20.9%) was not associated with chemotherapy response ( p = 0.62) or survival outcomes (PFS, p = 0.52; OS, p = 0.11). Only one (0.4%) case exhibited complete EDR to all tested drugs, and 74 (29.4%) cases showed no EDR. There was no statistical correlation between total number of drugs in the EDR range and chemotherapy response ( p = 0.55), progression-free survival (PFS) ( p = 0.18), and overall survival (OS) ( p = 0.87). Proportion of EDR, defined as the ratio of the number of EDR drugs divided by all drugs for an individual patient, was also not related to chemotherapy response ( p = 0.37), PFS ( p = 0.13), or OS ( p = 0.13). Conclusions Presence of extreme drug resistance to multiple agents in the in vitro drug resistance assays was not associated with survival outcomes in advanced stage epithelial ovarian, fallopian, and primary peritoneal cancers.

STANDARDIZED VISUAL ACUITY RESULTS ASSOCIATED WITH PRIMARY VERSUS SECONDARY BEVACIZUMAB (AVASTIN) TREATMENT FOR CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION

To compare standardized visual outcomes and macular thickness changes associated with primary and secondary bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) therapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Eighteen eyes received primary bevacizumab treatment; 20 eyes received pegaptanib (Macugen; Eyetech/OSI Pharmaceuticals, New York, NY) as initial treatment followed by bevacizumab therapy. Both medications were injected at 6-week intervals. Best-corrected visual acuity was measured with the ETDRS chart. Three- and 6-month data were analyzed for all eyes. Mean visual acuity improvement in the primary bevacizumab treatment cohort was 1.5 ETDRS lines at 3 months (P = 0.0009) and 2.2 ETDRS lines at 6 months (P=0.0004) compared with -0.4 ETDRS line at 3 months (P=0.27) and 0.2 ETDRS line at 6 months (P=0.70) in the secondary bevacizumab treatment group. Mean decrease in retinal thickness was also higher in the primary bevacizumab treatment group (90.9 microm [P=0.0037] vs 43.8 microm [P=0.13], respectively) than in the secondary bevacizumab treatment group (73.72 microm [P=0.051] vs 33.0 microm [P=0.21], respectively) at 3 months and 6 months. Primary bevacizumab therapy resulted in significantly greater visual improvement than secondary bevacizumab treatment at 3 months or 6 months. To our knowledge, this is the first report comparing primary bevacizumab treatment of CNV in AMD with secondary bevacizumab treatment after multiple pegaptanib injections.

Selective Laser Trabeculoplasty as Initial and Adjunctive Treatment for Open-Angle Glaucoma

To investigate the efficacy and safety of selective laser trabeculoplasty as an initial treatment for newly diagnosed open-angle glaucoma, and its role as adjunctive therapy. A prospective multicenter nonrandomized clinical trial was performed. Patients with newly diagnosed open-angle glaucoma or ocular hypertension were assigned to the primary (selective laser trabeculoplasty) treatment group or the control (latanoprost) group according to patient choice. Both groups were followed up at 1, 3, 6, and 12 months. A secondary treatment group was also included to study the efficacy of selective laser trabeculoplasty for patients intolerant of medical therapy or in whom such therapy was unsuccessful, with or without a history of previous argon laser trabeculoplasty. One hundred eyes (61 patients) were enrolled, 74 in the primary treatment group and 26 in the control group. The average absolute and percent reductions in intraocular pressure for the primary treatment group were 8.3 mm Hg or 31.0%, compared with 7.7 mm Hg or 30.6% for the control group (P = 0.208 and P = 0.879). The responder rates (20% pressure reduction) were 83% and 84% for the primary and control groups, respectively. There were no differences in intraocular pressure lowering with selective laser trabeculoplasty on the basis of angle pigmentation. A modest contralateral effect was observed in the untreated fellow eyes of patients undergoing selective laser trabeculoplasty. Selective laser trabeculoplasty was found to be equally efficacious as latanoprost in reducing intraocular pressure in newly diagnosed open-angle glaucoma and ocular hypertension over 12 months, independent of angle pigmentation. Nonsteroidal antiinflammatory therapy had similar efficacy to steroids after laser therapy. These findings support the consideration of selective laser trabeculoplasty as a first-line treatment for newly diagnosed open-angle glaucoma or ocular hypertension.

Combined Photodynamic Therapy and Intravitreal Triamcinolone Acetonide Injection for Neovascular Age-Related Macular Degeneration With Pigment Epithelium Detachment

To report the outcome of combined verteporfin photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for the treatment of choroidal neovascularization (CNV) with serous pigment epithelium detachment (PED) due to age-related macular degeneration (AMD). The files of all consecutive patients with CNV and serous PED who received PDT and IVTA either primarily (primary treatment group) or following previous unsuccessful PDT (secondary treatment group) were reviewed for visual and angiographic results. Ten patients (11 eyes) were included. Mean number of PDT sessions was 3.18; 8 eyes received one IVTA injection and 3 eyes received two IVTA injections. Thirty-six percent of patients retained their initial visual acuity after a mean follow-up of 15.3 months. Loss of 3 or more Snellen lines was noted in 2 of 3 eyes in the primary treatment group and 5 of 8 eyes in the secondary treatment group. Increased intraocular pressure developed in 3 patients and was controlled by topical medications. Although combined PDT and IVTA may be considered for CNV with serous PED in patients with poor prognosis with PDT alone, the regimen as administered in this small series was not beneficial. Further studies are required to determine whether alternate sequences, timing, or doses would yield a better outcome.

Qualitative and quantitative assessment of urinary cytokeratin 8 and 18 fragments compared with voided urine cytology in diagnosis of bladder carcinoma

Objectives To evaluate the value of urine tests based on the detection of cytokeratins 8 and 18 for the diagnosis of bladder cancer compared with urine cytology. Methods Samples from 112 patients before transurethral resection (group 1), 40 patients before secondary surgical treatment (group 2), 29 healthy control subjects (group 3, controls), and 10 women with acute urinary tract infection (group 4, controls) were examined with the UBC Rapid and UBC II enzyme-linked immunosorbent assay (ELISA) tests and voided urine cytology. Results Of the 112 patients in group 1, 90 had transitional cell carcinoma. For the UBC Rapid, UBC ELISA, and cytology, the sensitivity and specificity was 64.4%, 46.6%, and 70.5% and 63.6%, 86.3%, and 79.5%, respectively. The cytology had the greatest accuracy (72.3%) compared with both cytokeratin tests (54.4% and 64.2%). For all three tests, sensitivity increased with tumor grade and stage. In group 2, 16 of 40 patients had residual carcinoma. The sensitivity was similar for all three tests, and the specificity of cytology was lower compared with its specificity in group 1 (47.9% versus 70.5% in group 1). In the controls with or without urinary tract infection, the specificity of cytology was greater than that of both other tests. The combination of the UBC ELISA test with cytology increased the sensitivity to 83% (specificity 68%). Conclusions Both cytokeratin tests detected patients with transitional cell carcinoma, but were inferior to voided urine cytology in test quality.

Octreotide as Primary Therapy for Acromegaly

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB

Treatment of Advanced Prostatic Carcinoma with Estramustine Phosphate (Estracyt®)

Estramustine phosphate (Estracyt) was used in the treatment of 154 patients with carcinoma of the prostate in stage IV. Sixty-three patients were given Estracyt from the outset (primary treatment group) and 91 had previously received some other endocrine therapy (secondary treatment group). All of the patients were observed for more than one year. The drug was given intravenously and/or orally. Objective remissions occurred in 46 (73.0%) of the 63 patients in the primary treatment group and subjective remissions in all the objective responders and in 12 additional patients (92.0%). The corresponding figures for the secondary treatment group were 28 (30.7%) and 52 (57.1%) of 91. The side-effects were negligible, and the drug was well tolerated. No cumulative toxic effect was observed in patients who had been receiving the treatment for more than five years. In our opinion the compound is valuable in the treatment of advanced prostatic carcinoma (stage IV).

Combination chemotherapy of Hodgkin's disease.

Fifty-two patients with advanced Hodgkin's disease seen at the Massachusetts General Hospital since 1967 were treated with the MOPP (nitrogen mustard, vincristine, prednisone, and Procarbazine) combination. Of these patients, 35 had had no prior treatment, while 17 had relapsed after radiotherapy or single drug chemotherapy. The primary treatment group had a complete response rate of 91%, 66% of whom remain disease-free at a median remission duration exceeding 22 months. Complete responses occurred in 71% of the secondary treatment group, of whom 47% remain free of disease with a median in excess of 21 months. All Stage IIIA and IVA patients remain in complete remission, but 50% of those treated in Stage IIIB and IVB have relapsed. Relapses have occurred in 5 of 8 patients over the age of 50 years; bone marrow toxicity from MOPP was more severe in the older patients. Cancer 33:1499–1504, 1974.