[A Case of Descending Colon Cancer with Local Recurrence Eight Years and Seven Months after Curative Resection and Favorable Response to Pharmacotherapy-A Case Report].

A 73-year-old woman underwent a descending colectomy for descending colon cancer. The tumor was graded as pStage Ⅲb(pT3[SS], pN1b, pM0, Cur A), according to the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma. Postoperative treatment of adjuvant chemotherapy comprised oral tegafur/uracil and Leucovorin for 6 months with no evident recurrence. However, contrast-enhanced CT and FDG-PET/CT examination 8 years and 7 months after surgery revealed a 30 mm irregular recurrent tumor in the left iliac fossa. Since the tumor was adjacent to the left psoas muscle, it was considered that RM0(no tumor identified at the radial margin)could not be achieved in that region. Owing to the patient's good general condition, systemic chemotherapy with CAPOX+bevacizumab was administered. Although adverse events prompted discontinuation of the treatment during the first course, the recurrent tumor had significantly regressed. Systemic chemotherapy with mFOLFOX6+bevacizumab as selected subsequent treatment achieved a significant tumor shrinkage to date. Although a recurrence more than 5 years after curative resection of colorectal cancer is extremely rare, the possibility of late recurrence must be considered in patients with well-differentiated tumors who received adjuvant chemotherapy and had negative vascular invasion.

Management of macular oedema due to retinal vein occlusion: An evidence-based systematic review and meta-analysis.

BACKGROUND: Central retinal vein occlusion and branch retinal vein occlusion are common causes of visual loss due to associated macular oedema. The aim of this review was to assess the effectiveness of interventions improving vision and treating macular oedema in central retinal vein occlusion and branch retinal vein occlusion. METHODS: Medical search engines and clinical trial registries were systematically searched. Randomised clinical trials with ≥90 eyes and real-world outcome studies with ≥100 eyes each with ≥6 months follow-up were included. RESULTS: There were 11 randomised controlled trials evaluating treatments for central retinal vein occlusion which met the inclusion criteria and 10 for branch retinal vein occlusion. There were 10 real world outcome studies of central retinal vein occlusion and 5 real world outcome studies of branch retinal vein occlusion. Meta-analysis was performed on studies that met the defined inclusion criteria. Main outcomes were change in visual acuity at 6-, 12-, 24- and 36 months by treatment. CONCLUSIONS: Intravitreal anti-vascular endothelial derived growth factor is recommended as first line treatment over intravitreal corticosteroid due to its effectiveness and lower rate of ocular adverse events. Best outcomes are achieved when intravitreal treatment is started early. Macular laser may have an adjunctive role in branch retina vein occlusion but not central retinal vein occlusion.

Comparison of antihypertensive drugs amlodipine and perindopril on blood pressure variability after long-term treatment of hypertension induced by apatinib and bevacizumab.

The purpose of this study was to elucidate the therapeutic effect of different antihypertensive drugs (amlodipine and perindopril) on hypertension induced by apatinib and bevacizumab. Sixty patients with hypertension treated with apatinib or bevacizumab were selected and divided into two groups: one group was treated with amlodipine and the other group was treated with perindopril. Before and after treatment, the dynamic blood pressure (BP) measurement (systolic BP [SBP] and diastolic BP [DBP]), echocardiography (left ventricular end-diastolic diameter, interventricular septal thickness [IVST], left ventricular posterior wall thickness [LVPWT], and left atrial diameter [LAD]), and detection of nitric oxide (NO) content in venous blood were performed. In the amlodipine group, the 24hSBP, 24hSSD, 24hSCV, daytime mean SBP (dSBP), daytime mean SSD (dSSD), daytime mean SBP CV, night mean SBP (nSBP), night mean SSD, 24hDBP, 24hDSD, 24 h DBP CV, daytime mean DBP (dDBP), daytime mean DSD (dDSD), daytime mean DBP CV, night mean DBP (nDBP), LAD, and LAD index (LADi) after treatment were all lower than before treatment, while NO was higher than before treatment (all P < 0.05). In the perindopril group, the 24hSBP, dSBP, nSBP, 24hDBP, dDBP, nDBP, LAD, LADi, IVST, LVPWT, and left ventricular mass index (LVMI) after treatment were lower than before treatment, and NO level after treatment was higher than before treatment (all P < 0.05). After treatment, the 24hSBP, 24hSSD, dSBP, dSSD, nSBP, 24hDBP, 24hDSD, dDBP, dDSD, nDBP, night mean DSD, and NO were all lower while the LAD, LADi, IVST, LVPWT, and LVMI were higher in the amlodipine group than those in the perindopril group (all P < 0.05). Our study suggests that the SBP and DBP variability of amlodipine in the treatment of hypertension induced by apatinib and bevacizumab is slightly better than that of perindopril, but the effect of perindopril in improving endothelial function indices NO and echocardiographic data is better than that of amlodipine.

Treatment of pediatric cerebral radiation necrosis using hyperbaric oxygenation.

Introduction: Cerebral radiation necrosis is rarely encountered in pediatric patients. This case report describes a child with cerebral radiation necrosis who was successfully treated using corticosteroids, bevacizumab, and hyperbaric oxygenation. Case report: A 3-year-old boy developed progressive extremity weakness six months after the completion of radiation therapy for the treatment of a neuroepithelial malignancy. Treatment with corticosteroids and bevacizumab was initiated, but his symptoms did not improve, and he was then referred for hyperbaric oxygen therapy. After completing 60 hyperbaric treatments, he experienced significant improvements in mobility, which remained stable over the next year. Discussion: Cerebral radiation necrosis typically presents in children with symptoms of ataxia or headache. Corticosteroids and bevacizumab are common treatments, but hyperbaric oxygen therapy has also been studied as a therapeutic modality for this condition. When considering the use of hyperbaric oxygenation in pediatric patients, careful attention to treatment planning and patient safety can reduce the risks of adverse events such as middle ear barotrauma and confinement anxiety. Conclusion: In addition to other available pharmacologic therapies, hyperbaric oxygenation should be considered for the treatment of pediatric patients with cerebral radiation necrosis.

Refractory systemic capillary leak syndrome treated with bevacizumab: a case report.

Systemic capillary leak syndrome (SCLS) is a syndrome caused by many reasons and without a definitive mechanism. The main diagnostic criteria of SCLS are hemoconcentration, hypoalbuminemia, and hypotension. Though most SCLS improved spontaneously within a few days, it can be life-threatening without effective treatments. In previous literature, vascular endothelial growth factor (VEGF) inhibitor had shown its potential to be an effective treatment, but the treatment outcomes were inconsistent. This article was about a 58-year-old female suffering from refractory systemic capillary leak syndrome after bone marrow transplantation and being treated with bevacizumab, a VEGF inhibitor. In comparison with other successfully treated cases, this patient received four cycles of bevacizumab treatment without symptomatic improvement and eventually died in the intensive care unit. Further studies are needed to further confirm the role of bevacizumab in the management of SCLS.

Cost-minimisation analysis of a treat-and-extend regimen with anti-VEGFs in patients with neovascular age-related macular degeneration.

PURPOSE: Although intraocular anti-vascular endothelial growth factors (anti-VEGFs) are effective as treatment of neovascular age-related macular degeneration (nAMD), the (economic) burden on the healthcare system is considerable. A treat-and-extend (T&E) regimen is associated with a lower number of injections without compromising the effectiveness and can therefore help optimise nAMD treatment. This study investigates the per-patient costs associated with nAMD treatment, when using aflibercept, bevacizumab, or ranibizumab with a T&E regimen. METHODS: In this cost-minimisation model, the per-patient costs in the Netherlands were modelled using a healthcare payers' perspective over a 3-year time horizon with the assumption that efficacy of treatments is similar. Additionally, the break-even price of the different anti-VEGFs was calculated relative to the cheapest option and injection frequency. RESULTS: The injection frequency varied from 14.2 for aflibercept to 27.4 for bevacizumab in 3 years. Nonetheless, bevacizumab remains the cheapest treatment option (€14,215), followed by aflibercept (€18,202) and ranibizumab (€31,048). The medication covers the majority of the per-patient costs for aflibercept and ranibizumab, while administration covers the majority of the per-patient costs for bevacizumab. The break-even prices of aflibercept and ranibizumab are respectively €507 and €60.58 per injection. Brolucizumab was included in the scenario analysis and was more expensive than aflibercept (€20,446). Brolucizumab should reduce to 13.8 injections over 3 years to be as costly as aflibercept. CONCLUSION: Bevacizumab is the cheapest anti-VEGF treatment. The list prices of all anti-VEGFs should reduce to be as costly as bevacizumab. Aflibercept is the second-choice treatment and so far brolucizumab is not.

PANRETINAL PHOTOCOAGULATION VERSUS INTRAVITREAL BEVACIZUMAB VERSUS A PROPOSED MODIFIED COMBINATION THERAPY FOR TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Three-Arm Clinical Trial (CTPDR Study).

PURPOSE: To compare safety and therapeutic effect of three treatment protocols on patients with naive proliferative diabetic retinopathy. METHODS: A total of 207 eyes with proliferative diabetic retinopathy were randomly divided into three groups: full panretinal photocoagulation group; intravitreal bevacizumab (IVB) group with four monthly IVB injections; and modified combination group with two bimonthly IVB injections and a modified laser therapy. The best-corrected visual acuity and area of neovascularization leakage were compared at 1-year follow-up. RESULTS: The difference in final best-corrected visual acuity was not significant between the groups (P = 0.77). The modified combination group had the lowest final leakage area (P = 0.006). The difference in final mean deviation of visual field was not significant between IVB and modified combination groups (mean difference = 0.25, P = 0.23, 95% confidence interval, 0.12-1.38). There was no difference in rate of new-onset diabetic macular edema between IVB and modified combination groups (mean difference = 1.5%, P = 0.31, 95% confidence interval, 1.1-1.88). Mean of total IVB injections were 3.5, 7.4, and 6.2 for panretinal photocoagulation, IVB, and modified combination groups, respectively (P = 0.002). Patients in the IVB group underwent more visits (P = 0.001). In subgroup analysis, the difference in the final leakage area was significant for the eyes with diabetic macular edema (P = 0.005). CONCLUSION: A combination protocol of photocoagulation and IVB can be recommended for proliferative diabetic retinopathy, especially with baseline diabetic macular edema.

Clinical Efficacy of Bevacizumab Plus XELOX Chemotherapy in Colorectal Cancer and Application Value of Mindfulness-Based Stress Reduction Intervention.

Background and Objectives: Colorectal cancer (CRC) is a malignant tumor with an extremely high incidence rate worldwide. This study explores the influence of mindfulness-based stress reduction (MBSR) in the care of patients with CRC undergoing bevacizumab (BVZ) plus XELOX chemotherapy, aiming at providing reliable reference and guidance for further improving their rehabilitation and prognosis. Methods: Between January 2019 and March 2020, 88 patients with CRC admitted consecutively to Jiangsu Cancer Hospital in China were enrolled in the study. Of them, 42 patients receiving BVZ plus XELOX chemotherapy, conventional care and MBSR intervention were assigned to the intervention group, and the remaining 46 patients receiving XELOX chemotherapy and conventional care were included in the control group. Clinical efficacy, safety and improvement in functional status were compared. Patients' psychological state, treatment compliance and self-care ability were evaluated. Finally, prognostic quality of life (QoL) was recorded at 1-year follow-up. Results: The overall response rate and incidence of adverse events in the intervention group were not different in the control group, but the total control rate and improvement rate in the intervention group were higher. After treatment, Sedation-Agitation Scale (SAS) and Self-Rating Depression Scale (SDS) scores in the intervention group were decreased, compliance and self-care ability were improved, all of which were better than in the control group. Prognostic follow-up showed that the QoL in the intervention group was also higher than in the control group. Conclusions: The combined use of BVZ in XELOX-based chemotherapy can improve the clinical outcome and functional status of patients with CRC. In addition, MBSR intervention implemented during chemotherapy can effectively optimize patients' psychological state and treatment compliance, strengthen their self-care ability and improve their prognostic QoL.

Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial.

Importance: Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments. Objective: To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment. Design, Setting, and Participants: This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021). Interventions: Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified. Main Outcomes and Measures: The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%. Results: Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators. Conclusions and Relevance: Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT04004208.

Clinical variations and therapeutic challenges in the management of symptomatic retinal artery macroaneurysm: a tertiary center experience.

PURPOSE: To find out clinical characteristics, therapeutic options, and visual outcome in symptomatic retinal artery macroaneurysm (RAMA) patients. METHOD: Newly diagnosed cases of symptomatic RAMA from January 2015 to December 2019 were included. Fifteen eyes of 15 patients with mean age 62.46 years ± 14.89 (SD) fulfilled the inclusion criteria. RESULT: Hypertension was present in 66.6% of the patients, and the commonest site was superotemporal (12 eyes, 80%). The most commonly employed treatment was Nd: Yag laser hyaloidotomy in 4 eyes (26.6%). Other treatments were intravitreal bevacizumab in 3 eyes (20%), focal laser with intravitreal bevacizumab in 3 eyes (20%), PPV with focal laser (13.3%) in 2, focal laser only in one (6.6%), PPV with focal and intravitreal bevacizumab in one (6.6%). The mean best-corrected visual acuity (BCVA) at baseline was 1.35 ± 0.84 LogMAR, which improved to 0.39 ± 0.53 LogMAR at the last follow-up. Presenting VA 0.77 (±0.40) improved to 0.20 (±0.17) p value (0.180) in intravitreal bevacizumab only group, 1.29 (±0.35) to 0.75 (±0.15) p value 0.66 in Nd: Yag laser group, 2.67 (±0.58) to 0.46 (±0.28) p value 0.019 in PPV group and did not improve in combined anti-VEGF and focal laser group due to dense hard exudates at the fovea in one and persistent cystoid macular edema in another case. CONCLUSION: With regard to its presentation, which can vary tremendously, there are no approved guidelines for its treatment. The present study reinforces the need for a treatment guideline development. Customization of treatment should be considered depending on the clinical presentation of each case.

[Possibility of Prolonging Treatment by Preventing Paclitaxel-Induced Peripheral Neuropathy Using Compression Therapy].

We evaluated the efficacy of surgical glove(SG)-compression therapy for paclitaxel (PTX)-induced peripheral neuropathy (PN)and the impact of PN prevention on treatment duration. Patients with advanced or metastatic breast cancer underwent a combined treatment of PTX and bevacizumab with(n=20; patients wore 2 SGs for 120 min)or without(n=15) compression therapy. SG-compression therapy significantly decreased the incidence of Common Terminology Criteria for Adverse Events(CTCAE)v4.0 Grade 2 or higher PN by 71.9% and prolonged time-to-treatment-failure(TTF)of PTX from 200 to 240 days. SG-compression therapy was effective for PTX-induced PN and may have prolonged the TTF of PTX.

[Prevention of intraocular pressure elevation following intravitreal injections]. / Profilaktika povysheniya urovnya vnutriglaznogo davleniya posle intravitreal'nykh in"ektsii.

Determining the role of vascular endothelial growth factor (VEGF) in the pathogenesis of intraocular neovascularization prompted the development of anti-VEGF therapy. In general, these intravitreal injections (IVI) are considered relatively safe. One of the side effects that can occur after IVI of anti-VEGF agents is ocular hypertension, it can be acute or persistent. Numerous studies investigating the prevention of ophthalmic hypertension have been carried out in connection with the proven risk of short-term intraocular pressure (IOP) elevation after anti-VEGF injections. Scientific literature describes several methods of preventing intraocular pressure spikes after IVI: prophylactic medications, anterior chamber paracentesis, scleral decompression. Despite the significant number of publications, there is no universal consensus on the necessity of prevention measures for IVI of anti-VEGF drugs since the clinical benefits of slightly reducing the short-term IOP spikes remain unclear. This literature review analyzes the prospects of preventing ocular hypertension after IVI of anti-VEGF agents.

Bevacizumab vs laser interstitial thermal therapy in cerebral radiation necrosis from brain metastases: a systematic review and meta-analysis.

PURPOSE: Radiation necrosis (RN) represents a serious post-radiotherapy complication in patients with brain metastases. Bevacizumab and laser interstitial thermal therapy (LITT) are viable treatment options, but direct comparative data is scarce. We reviewed the literature to compare the two treatment strategies. METHODS: PubMed, EMBASE, Scopus, and Cochrane databases were searched. All studies of patients with RN from brain metastases treated with bevacizumab or LITT were included. Treatment outcomes were analyzed using indirect meta-analysis with random-effect modeling. RESULTS: Among the 18 studies included, 143 patients received bevacizumab and 148 underwent LITT. Both strategies were equally effective in providing post-treatment symptomatic improvement (P = 0.187, I2 = 54.8%), weaning off steroids (P = 0.614, I2 = 25.5%), and local lesion control (P = 0.5, I2 = 0%). Mean number of lesions per patient was not statistically significant among groups (P = 0.624). Similarly, mean T1-contrast-enhancing pre-treatment volumes were not statistically different (P = 0.582). Patterns of radiological responses differed at 6-month follow-ups, with rates of partial regression significantly higher in the bevacizumab group (P = 0.001, I2 = 88.9%), and stable disease significantly higher in the LITT group (P = 0.002, I2 = 81.9%). Survival rates were superior in the LITT cohort, and statistical significance was reached at 18 months (P = 0.038, I2 = 73.7%). Low rates of adverse events were reported in both groups (14.7% for bevacizumab and 12.2% for LITT). CONCLUSION: Bevacizumab and LITT can be safe and effective treatments for RN from brain metastases. Clinical and radiological outcomes are mostly comparable, but LITT may relate with superior survival benefits in select patients. Further studies are required to identify the best patient candidates for each treatment group.

Identifying response in colorectal liver metastases treated with bevacizumab: development of RECIST by combining contrast-enhanced and diffusion-weighted MRI.

OBJECTIVES: Response evaluation criteria in solid tumors (RECIST) often fail to identify clinically meaningful response to bevacizumab-containing therapy in colorectal liver metastasis (CRLM). This study aimed to develop RECIST by combining contrast-enhanced and diffusion-weighted magnetic resonance imaging (MRI). METHODS: A total of 126 patients with CRLM who underwent hepatic resection after bevacizumab-containing chemotherapy were split into initial analyses cohort (N = 42, with 76 indexed liver metastases) and validation cohort (N = 84). In lesion-based analyses, percentage decrease of arterial enhancement area and percentage increase of apparent diffusion coefficient (ADC) value from baseline to post-chemotherapy were measured. Their optimal cutoff values for distinguishing pathology-confirmed major and minor response were determined. Then, the developed RECIST (D-RECIST) was established by combining functional and size-based items. Survival relevance of D-RECIST and RECIST was examined in the validation cohort. RESULTS: Percentage decrease of arterial enhancement area and increase of ADC value significantly differed between lesions of pathologic major or minor response, with optimal cutoffs of approximately 33% and 19%, respectively. Patients defined as responders by D-RECIST had a significantly longer median disease-free survival (DFS) than non-responders (p = 0.021; 12.9 versus 8.6 months). No significant difference was observed with RECIST (p = 0.524). In a Cox regression model, D-RECIST- but not RECIST-defined responses independently predicted the DFS (p = 0.034 and 0.811). CONCLUSIONS: D-RECIST-defined responses provided significant prognostic information, and thus may serve as a better response evaluation approach than RECIST in CRLM treated with bevacizumab-containing therapy. KEY POINTS: • Changes in arterial enhancement area and apparent diffusion coefficient value are associated with pathological response in colorectal liver metastases treated with bevacizumab. • The MRI-based response criteria developed by combining size-based and functional features can provide significant prognostic information.

Complications of retinopathy of prematurity treatment.

PURPOSE OF REVIEW: The purpose of this review is to summarize complications of treatment for retinopathy of prematurity (ROP) and to compare complications of laser and intravitreal antivascular endothelial growth factor (VEGF) injections. RECENT FINDINGS: Poor structural outcomes and myopia are more common with laser for severe ROP than with anti-VEGF. Clinical trial data show unfavourable outcomes in 9.1-9.5% of laser treated, and 1.4-3.6% of anti-VEGF treated eyes. Additional randomized trial data show risk for very high myopia (≥-8.00D) to be 3.8 and 51.4% for zone I eyes treated with bevacizumab and laser, respectively. However, anti-VEGF may be complicated by late recurrence and is more likely to require retreatment than laser. Laser often necessitates general anaesthesia with its attendant risks, including worse short-term respiratory outcomes. Neurodevelopmental complications have been reported with anti-VEGF, but existing studies are subject to bias. SUMMARY: Treatment complications are substantially different for the two modalities in common use today. In more severe cases, risk of poor structural outcome and myopia favour treatment with anti-VEGF. In less severe ROP, risk of recurrence and the need for additional treatments may favour laser. Additional data are needed to establish comparative risks of neurodevelopmental complications.

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial.

INTRODUCTION: The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial. METHODS: In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated. RESULTS: From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61). CONCLUSIONS: In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis. TRIAL REGISTRATION NUMBER: NCT01706120.

Acute Heart Failure in a Patient with Occult Barlow's Disease Receiving Bevacizumab.

Bevacizumab is a recombinant humanized monoclonal antibody and a key drug for treatment of various types of cancer. Bevacizumab is associated with the occurrence of heart failure, but its risk factors remain unknown. A 55-year-old woman was diagnosed with cervical cancer, which was completely treated by bevacizumab-incorporated chemotherapy. During the 9-month bevacizumab therapy, she suffered from hypertension requiring multiple antihypertensive agents. She was admitted to our hospital due to acute heart failure with afterload mismatch and severe mitral regurgitation. A transesophageal echocardiography showed Barlow's disease with a degenerated and widely prolapsed mitral valve. She received a scheduled surgical mitral valve repair. Post-operative cause was uneventful, but metastatic dissemination developed later. The existence of mitral valve regurgitation, even when sub-clinical, might be a risk of worsening heart failure during bevacizumab therapy. Careful follow-up at an onco-cardiology clinic is highly encouraged particularly for such a cohort during bevacizumab therapy.

Intravitreal injections of anti-VEGF agents during COVID-19 pandemic: clinical audit from Tanta University Hospital.

BACKGROUND: The aims of this study were to provide real-life data about the effect of COVID-19 pandemic on the practice of anti-VEGF injections and to evaluate the safety of the modifications in the injection protocol imposed during the ongoing pandemic on the anatomical and functional outcome of patients. METHODS: All patients attending Tanta University hospital for receiving intravitreal anti-VEGF injections were screened. Patients who were previously deferred according to a modified protocol implemented in the hospital in response to the pandemic or who demonstrated deviation from it were included for further analysis. RESULTS: During the audit period, 83 patients attending for anti-VEGF injections were screened, of whom 40 met the abovementioned criteria and were included for analysis. In the deferred subgroup (11 eyes), predeferral mean values of logMAR best corrected visual acuity (BCVA) and central retinal subfield thickness (CST) were 1 ± 0.23 and 444.57 ± 200.1 µm, respectively. There was no significant change when the patients returned for their deferred injections, with the mean BCVA and CST values being 0.8 ± 0.22 and 413.71 ± 237.7 µm, respectively (p = 0.27 and p = 0.12). Moreover, 29 patients encountered a disturbed injection schedule, particularly skipping their injection appointments due to infection fear as found in 18 patients. CONCLUSION: The COVID-19 pandemic has imposed pressing challenges in maintaining essential health care while ensuring the prevention of spread of infection. Although the modified injection protocol confirmed to be safe for patients, the pandemic caused deflection from the optimum practice in the form of successive skipping of appointments and delays in the processing of patient injection schedules.

Study on the clinical effects of targeted therapy on elderly patients with gastric cancer.

To explore the clinical effects of targeted drug therapy on elderly patients with gastric cancer. Totally 200 metastatic gastric cancer patients who came to our hospital from January 2017 to January 2020 were selected and randomized into four groups, with 50 patients in each group. Bevacizumab (Group I), apatinib (Group II), and recombinant human endostatin (Group III) adopted respectively. While the control group received no targeted drug. Clinical data and clinical effect was collected and compared. After the therapy, the vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-2 (sVEGFR2) and human epithelial growth factor receptor-2 (HER2) positive detection of Group I, Group II, and Group III were better than the control group (P<0.05). In addition, the therapeutic effects of Group I, Group II, and Group III were higher and the incidence of adverse reactions was lower than the control group (P<0.05). Targeted drugs have obvious clinical effects in gastric cancer. It can effectively inhibit tumor growth and reduce the occurrence of complications, which is worthy of extensive clinical application and promotion.

Phase I Study of Alternate-Day Administration of S-1, Oral Leucovorin, and Bevacizumab for Refractory Metastatic Colorectal Cancer.

LESSONS LEARNED: The recommended S-1 dose was 40 mg/m2 , twice daily on Monday, Wednesday, Friday, and Sunday, with oral leucovorin and bevacizumab. Compared with daily administration, the alternate-day administration of S-1 with oral leucovorin may reduce mucositis with promising antitumor activity in refractory metastatic colorectal cancer. BACKGROUND: Daily S-1 plus oral leucovorin administration in a 1-week-on/1-week-off schedule has promising efficacy in gastrointestinal cancer but is associated with high risk of mucositis and diarrhea. METHODS: This phase Ib, 3+3 dose-escalation trial included patients with chemorefractory metastatic colorectal cancer (mCRC) receiving S-1 (40 mg/m2 ) and leucovorin (25 mg) orally twice daily (level 1, even-numbered days; level 2, Monday, Wednesday, Friday, and Sunday) and intravenous bevacizumab (5 mg/kg) every 2 weeks. Enrollment continued at the recommended dose level in the expansion cohort. RESULTS: We enrolled 21 patients (3 and 18 patients in levels 1 and 2, respectively). Briefly, 12 and 9 patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 and 1, respectively, and 8 and 13 patients had 1-3 and ≥4 prior treatment lines, respectively. Dose-limiting toxicity (DLT) was not observed, and level 2 was confirmed as the recommended dose. Common grade 3-4 adverse events at level 2 were anemia (22%), anorexia (6%), and diarrhea (6%). In the entire cohort, response rate, disease control rate, and median progression-free survival were 10%, 71%, and 4.2 months, respectively. CONCLUSION: The recommended S-1 dose was 40 mg/m2 , twice daily on Monday, Wednesday, Friday, and Sunday, with 25 mg oral leucovorin twice daily and 5 mg/kg bevacizumab every 2 weeks. Compared with the daily administration, alternate-day administration of S-1 plus leucovorin may reduce mucositis with promising antitumor activity in refractory mCRC.