Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial. Randomized controlled trial of combined 5-Fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy. Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 2. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Portal vein chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in 10 studies. Liver Infusion Meta-analysis Group. A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis. Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. A randomized, prospective trial of deep venous thrombosis prophylaxis in aortic surgery.
To assess the safety and efficacy of adjuvant combination therapy using 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) for prevention of proliferative vitreoretinopathy (PVR) after vitrectomy and retinal reattachment surgery.
                Prospective randomized, double-masked, placebo controlled trial.
                One hundred seventy-four high-risk patients were randomized to receive either 5-FU and LMWH therapy or placebo. Patients were selected from all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment.
                Results of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up.
                Development of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity.
                There were 87 patients in the 5-FU and LMWH therapy group and 87 in the placebo group. The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group. In 26.4% (23/87) of the placebo group and in 12.6% (11/87) of the 5-FU and LMWH group, postoperative PVR developed. In the 5-FU and LMWH group, the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations resulting from PVR was 52.9% (9/17). In the placebo group, the number of patients undergoing more than one operation was 25.3% (22/87) and the number of reoperations resulting from PVR was 72.7% (16/22). The difference in visual acuity was not statistically different in the two treatment groups, although those patients in whom postoperative PVR developed tended to have poorer vision (P < 0.0001). There were no differences in complication rates between the two groups.
                There is a significant reduction in the incidence of postoperative PVR in patients receiving the 5-FU and LMWH therapy and in the reoperation rate resulting from PVR. This trial shows that incidence of PVR can be reduced with inexpensive and simple pharmacologic treatment with 5-FU and LMWH and should be used routinely in the treatment of patients at risk of developing PVR. To determine the efficacy of a combination of 5-fluorouracil (5FU) and low-molecular-weight heparin (LMWH) in the treatment of unselected rhegmatogenous retinal detachment (RRD) undergoing primary vitrectomy.
                Double-masked, prospective, randomized, placebo-controlled clinical trial.
                Six hundred forty-one patients presenting with primary RRD were recruited from 2 specialized vitreoretinal units-Moorfields Eye Hospital, London (n = 553) and St. Pauls Eye Unit, Liverpool (n = 88).
                All patients underwent primary vitrectomy and gas endotamponade. Adjuvant therapy in the treatment group consisted of 5 IU/ml LMWH and 200 mug/ml 5FU added to the perioperative infusion fluid.
                The primary outcome measure was retinal reattachment after primary vitrectomy without any reoperations at 6 months. Secondary outcome measures recorded at 6 months were the occurrence and grade of proliferative vitreoretinopathy (PVR), best-corrected visual acuity in logarithm of the minimum angle of resolution, intraocular pressure (mmHg), corneal clarity, and complications.
                The overall primary success rate was 84.4%; in the treatment group, the primary success rate was 82.3% compared with 86.8% in the placebo group (P = 0.12). At 6 months, the final complete anatomical reattachment rate was 97.9% in both treatment and placebo groups. The number of patients who failed due to the development of PVR was not statistically significant, 23 in the treatment group (7.0%) and 14 in the placebo group (4.9%) (P = 0.309). There was no significant difference in the mean visual acuity at 6 months in the placebo group (0.48) versus the treatment group (0.53; P = 0.072). The visual acuity at 6 months of patients presenting with a macula-sparing retinal detachment was significantly worse in the treatment group (P = 0.0091). There was no significant difference between the 2 groups in patients who presented with a macula involving retinal detachment (P = 0.896).
                Primary vitrectomy has a high anatomic and visual success rate for RRD. Adjuvant therapy with 5FU and LMWH does not improve the anatomic or visual success rate of unselected primary retinal detachments undergoing vitrectomy. After adjuvant therapy, a worse visual outcome was observed in patients presenting with macula-sparing retinal detachments. A combination of 5FU and LMWH should not be used routinely for primary RRD surgery. Between September 1987 and October 1990, 265 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy were treated with vitrectomy and randomized to treatment with perfluoropropane gas or silicone oil; 131 eyes had undergone no prior vitrectomy (group 1) while 134 eyes had undergone vitrectomy with intraocular gas tamponade (group 2). At the last examination, there were no differences between perfluoropropane gas and silicone oil in achieving visual acuity greater than or equal to 5/200 (43% vs 45% for group 1, 38% vs 33% for group 2) and complete posterior retinal reattachment (73% vs 64% for group 1, 73% vs 61% for group 2). For group 1 eyes followed up for at least 18 months, there was an advantage favoring perfluoropropane gas in achieving complete posterior retinal reattachment (83% vs 60% at 36 months, P = .045). The rates of reoperation and keratopathy were similar, while hypotony was more prevalent in eyes randomized to perfluoropropane gas (group 2). Regardless of tamponade, groups 1 and 2 had similar anatomic and visual success. However, hypotony was twice as prevalent in group 2 (perfluoropropane), and the prevalence of keratopathy increased with follow-up in group 2 (either tamponade). Either tamponade produced better results than those seen with sulfur hexafluoride gas (Silicone Study Report 1). To evaluate the effect of preoperative intravitreal bevacizumab (IVB) injection on the rate of early (< or =4 weeks) postvitrectomy hemorrhage in patients with proliferative diabetic retinopathy (PDR).
                Prospective, randomized, double-masked clinical trial.
                Sixty-eight eyes of 68 patients undergoing pars plana vitrectomy for management of PDR complications.
                Eligible eyes were assigned randomly to 1 of 2 groups: the IVB group received 1.25 mg intravitreal bevacizumab 1 week before surgery, and the control group underwent a sham procedure.
                The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in best-corrected visual acuity (BCVA) and IVB-related adverse events.
                Of 68 eyes, 35 and 33 eyes were in the IVB and control groups, respectively. In the intention-to-treat analysis, the incidence of postvitrectomy hemorrhage 1 week and 1 month after surgery was significantly lower in the IVB group compared with the control group (P = 0.023 and P = 0.001, respectively). Mean BCVA improved from 1.88 logarithm of minimum angle of resolution (logMAR) units in both study groups before surgery to 0.91 logMAR units and 1.46 logMAR units 1 month after vitrectomy in the IVB and control groups, respectively (P = 0.001). Resolution of vitreous hemorrhage was observed in 9 eyes (25.7%) after IVB injection, obviating the need for vitrectomy; the corresponding figure was 2 eyes (6.1%) in the control group (P = 0.028). The per-protocol analysis included 16 eyes in the IVB group and 18 eyes in the control group; postvitrectomy hemorrhage occurred less frequently 1 week and 1 month after surgery in the IVB group compared with the control group (P = 0.033 and P = 0.003, respectively). Mean improvement in BCVA 1 month after vitrectomy was -1.05 logMAR units in the IVB group and -0.42 logMAR units in the control group (P = 0.004). No IVB-related complication was observed in the treatment group.
                Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. The need for vitrectomy also may be decreased significantly in these cases. Systemic delivery of cytotoxic drugs yields relatively low doses in the liver, a major site of recurrence for colorectal cancer. Giving chemotherapy by means of continuous portal vein infusion (PVI) into the liver during the immediate postoperative period may improve therapeutic efficacy.
                We undertook a meta-analysis to assess the effects on recurrence and survival of administering fluorouracil (5-FU)-based chemotherapy by PVI after colorectal cancer surgery.
                Data on mortality and recurrence were sought for all patients enrolled in randomized trials initiated before 1987 in which a few days (range, 5-7 days) of continuous postoperative PVI of cytotoxic drugs was compared with no further treatment. Data from 10 trials (a promising initial study and nine hypothesis-testing trials) involving about 4000 patients were available for analysis. The main cytotoxic drug in each trial was 5-FU (given with heparin); however, mitomycin C was co-administered in two of the trials. Four trials included an additional control group of patients treated with continuous noncytotoxic PVI of either heparin or urokinase alone; one trial included a second control group of patients treated with continuous systemic infusion of 5-FU. Reported P values are two-sided.
                Among the 3499 patients randomly assigned to receive either cytotoxic PVI or no further treatment, 1557 deaths are known to have occurred. Survival with and without PVI appeared to be the same for the first 2 years; thereafter, it diverged significantly, with the absolute survival difference (i.e., improvement) associated with PVI at 5 years being 4.7 % (standard deviation [SD] = 1.2 %) (P = .006). When just the nine hypothesis-testing trials were considered, the absolute survival difference was 3.6% (SD = 1.2%) (P = .04). If, ignoring any potential for bias in stage assignment, attention was restricted to patients with Dukes' stage A, B, or C disease (88.3% of the total), the absolute effect on 5-year survival for all 10 trials increased to 6.0% (SD = 1.8%) (P = .001); this estimate remained statistically significant when the initial study was excluded (absolute survival difference = 4.8%; SD = 1.8%; P = .01). In contrast to the highly significant reduction in liver metastases seen in the initial study (79% reduction; SD = 15%; P = .00000007), the reduction found in the nine hypothesis-testing trials was not significant (14% reduction; SD = 10%; P = .2). In the trials with additional control groups, survival appeared to be better with cytotoxic PVI than with noncytotoxic PVI or with systemic cytotoxic drug infusion.
                PVI of 5-FU (with or without other cytotoxic drugs) for about 1 week after surgery in patients with colorectal cancer may produce an absolute improvement in 5-year survival of a few percent. Although encouraging, this finding is not statistically secure, and additional evidence from randomized trials involving several thousand more patients is needed. To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).
                A randomised, open-label trial.
                In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.
                During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.
                Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer. To evaluate the use of preoperative intravitreal bevacizumab (IVB) in patients undergoing pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy (PDR).
                We studied 22 patients with severe PDR. A preoperative complexity score (CS) was recorded. Eleven eyes were treated with IVB, 1.25 mg, 5-7 days before PPV (group 1), and 11 eyes underwent direct PPV (group 2). Surgical time and intra-operative manoeuvres were recorded. Main outcome measure was feasibility of surgery, secondary goal was the visual and anatomic outcome at 6 months.
                The average CS was 5.5, and was similar in the two groups. Mean surgical time was 57 minutes in group 1 vs 83 minutes in group 2; mean tool exchanges was 27 vs 53, intraoperative bleeding 5 vs 15, endodiathermy 2 vs 9. No complications were recorded after IVB. Mean pre-operative BCVA was 1.87 logMAR in group 1 and logMAR 2.04 in group 2. Mean pre-operative BCVA was 1.87 logMAR in the bevacizumab group and 2.04 logMAR in group 2, not significantly different (p = 0.7). Mean post-operative BCVA at 6 months was 0.88 logMAR in group 1 and logMAR 2.01 in control group 2, significantly different (p = 0.01). Post-operative BVCA improved in bevacizumab group from pre-operative value (p = 0.15), while in control group there was non-significant increase (p = 0.96). Anatomical attachment was achieved in 11 patients in group 1 vs nine patients in group 2.
                IVB administered prior to vitrectomy was well tolerated and reduced active neovascularization, thus facilitating PPV. The purpose of this study is to evaluate the role, the safety and the effectiveness of intravitreal bevacizumab (IVB) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy (PDR).
                Case-Control Study
                Randomized controlled trial performed on 72 eyes of 68 patients affected by vitreous haemorrhage (VH) and tractional retinal detachment (TRD), which occurred as a consequence of active proliferative diabetic retinopathy (PDR). We randomly assigned eligible patients in a 1: 1: 1 ratio to receive a sham injection or an intravitreal injection of 1.25 mg of bevacizumab, either 7 or 20 days before the vitrectomy. In order to obtain three homogeneous groups of surgical complexity, we assigned to the following preoperative parameters a score from 0 to 3: a) vitreous haemorrhage, b) prior retinal laser-photocoagulation, c) morphological types of retinal detachment such as focal, hammock, central diffuse, table-top. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12, and 24 weeks after the surgery.
                Intraoperative management, safety, efficacy of IVB at different time injection as an adjunct to vitrectomy in the management of severe PDR RESULTS: Group A (sham injection): intraoperative bleeding occurred in 19 cases (79.1%), the use of endodiathermy was necessary in 13 patients (54.1%), relaxing retinotomy was performed on one patient (4.1%), and in four cases (16.6%) iatrogenic retinal breaks occurred. The surgical mean time was 84 minutes (SD 12 minutes). Group B (bevacizumab administered 7 days before vitrectomy): intraoperative bleeding occurred in two cases (8.3%) and the use of endodiathermy was necessary in two patients (8.3%). No iatrogenic breaks occurred during the surgery. The surgical mean time was 65 minutes (SD 18 minutes). Group C (bevacizumab administered 20 days before vitrectomy): intraoperative bleeding occurred in three cases (12.5%), the use of endodiathermy was necessary in three patients (1.5%), and an iatrogenic break occurred in one patient (4.1%) while the delamination of fibrovascular tissue was being performed. The surgical mean time was 69 minutes (SD 21 minutes). The average difference in the surgical time was statistically significant between group A and group B (p = 0.025), and between group A and group C (p = 0.031). At the end of the surgery, the retina was completely attached in all eyes. At the 6-month follow-up, we observed the development of tractional retinal detachment (TRD) in one out of 24 patients from group C (4%).
                A preoperative intravitreal injection of bevacizumab may represent a new strategy for the surgical treatment of severe PDR by reducing retinal and iris neovascularization: this would make surgery much easier and safer, thus improving the anatomical and functional prognosis. According to our study, the best surgical results are achieved performing the IVB 7 days preoperatively. To study the incidence of postoperative deep venous thrombosis (DVT) in patients undergoing elective aortic reconstruction and to determine if aggressive DVT prophylaxis would reduce the incidence of DVT in these patients.
                Randomized, prospective trial.
                University hospital and Veterans Affairs hospital.
                One hundred patients undergoing aortic reconstruction for aneurysmal or occlusive disease randomized to receive DVT prophylaxis (treatment group) or no prophylaxis (control group). Exclusion criteria included a history of DVT, long-term anticoagulant use, or a malignant neoplasm. During the study period, 12 patients were ineligible for follow-up. Ninety-eight patients completed the trial, including 50 patients in the treatment group and 48 patients in the control group. Two patients in the control group died postoperatively of unrelated causes.
                Patients in the treatment group received DVT prophylaxis using a combination of low-dose heparin sodium therapy (5000 U every 12 hours) and calf-length intermittent mechanical compression devices. Control patients received no DVT prophylaxis.
                The occurrence of acute lower extremity DVT diagnosed by interval venous duplex ultrasound scan surveillance performed on postoperative days 1, 3, and 7.
                The overall incidence of proximal DVT in this study was 2%. One case of DVT occurred in the treatment group, and the other one occurred in the control group. There was no statistically significant difference (P = .99) in the incidence of DVT between the 2 groups. One patients in the control group had a nonfatal pulmonary embolus (1% of the patients overall).
                The incidence of proximal DVT in patients undergoing elective aortic reconstruction is low compared with patients undergoing other major intraabdominal general surgical procedures. The use of aggressive DVT prophylaxis did not reduce the risk of postoperative proximal DVT in this study. The selective use of DVT prophylaxis in patients undergoing elective aortic surgery should be based on associated concomitant or evolving risk factors.
Results from this review indicate that there is inconsistent evidence from two studies on patients at different risk of PVR on the effect of LMWH and 5-FU used during vitrectomy to prevent PVR. Future research should be conducted on high risk patients only, until a benefit is confirmed at least in this patient subgroup.