The role for intra-arterial chemotherapy for refractory retinoblastoma: a systematic review

Background Intra-arterial chemotherapy is a new retinoblastoma treatment associated with high rates of globe salvage that has been widely adopted for primary treatment of retinoblastoma but is less frequently used as secondary treatment for refractory retinoblastoma. This systematic review aims to summarize the reported outcomes of intra-arterial chemotherapy for refractory retinoblastoma. Methods We conducted a systematic review of studies published on PubMed, Medline, and Embase from 2011 to 2021 reporting globe salvage rates following intra-arterial chemotherapy for secondary treatment of refractory retinoblastoma. Results Our search yielded 316 studies, and 24 met inclusion criteria. The 24 included studies were comprised of 1366 patients and 1757 eyes. Among these, 1184 (67%) eyes received secondary indication treatment, and globe salvage was achieved for 776 of these 1184 eyes (64%). Sixteen studies reported cannulation success rates from 71.8 to 100%. Pooled analysis of subjects revealed 21 patients (2.6%) with metastatic disease and 26 deaths (3%) during study follow-up periods (7–74 months). The most common ocular complications were vitreous hemorrhage (13.2%), loss of eyelashes (12.7%), and periocular edema (10.5%). The most common systemic complications were nausea/vomiting (20.5%), neutropenia (14.1%), fever (8.2%), and bronchospasm (6.2%). Conclusions Intra-arterial chemotherapy is associated with high rates of globe salvage and low rates of serious complications in patients with refractory retinoblastoma. Unfortunately, current literature is predominantly comprised of retrospective case studies, and further high-quality evidence is necessary to inform clinical practice (AU)

The role for intra-arterial chemotherapy for refractory retinoblastoma: a systematic review.

BACKGROUND: Intra-arterial chemotherapy is a new retinoblastoma treatment associated with high rates of globe salvage that has been widely adopted for primary treatment of retinoblastoma but is less frequently used as secondary treatment for refractory retinoblastoma. This systematic review aims to summarize the reported outcomes of intra-arterial chemotherapy for refractory retinoblastoma. METHODS: We conducted a systematic review of studies published on PubMed, Medline, and Embase from 2011 to 2021 reporting globe salvage rates following intra-arterial chemotherapy for secondary treatment of refractory retinoblastoma. RESULTS: Our search yielded 316 studies, and 24 met inclusion criteria. The 24 included studies were comprised of 1366 patients and 1757 eyes. Among these, 1184 (67%) eyes received secondary indication treatment, and globe salvage was achieved for 776 of these 1184 eyes (64%). Sixteen studies reported cannulation success rates from 71.8 to 100%. Pooled analysis of subjects revealed 21 patients (2.6%) with metastatic disease and 26 deaths (3%) during study follow-up periods (7-74 months). The most common ocular complications were vitreous hemorrhage (13.2%), loss of eyelashes (12.7%), and periocular edema (10.5%). The most common systemic complications were nausea/vomiting (20.5%), neutropenia (14.1%), fever (8.2%), and bronchospasm (6.2%). CONCLUSIONS: Intra-arterial chemotherapy is associated with high rates of globe salvage and low rates of serious complications in patients with refractory retinoblastoma. Unfortunately, current literature is predominantly comprised of retrospective case studies, and further high-quality evidence is necessary to inform clinical practice.

A double-masked, randomized, placebo-controlled trial of temporary endoscopic mucosal gastric electrical stimulation for gastroparesis.

BACKGROUND: Endoscopically placed, temporary gastric electrical stimulation (tGES) may relieve symptoms of gastroparesis (Gp) and predict permanent gastric electrical stimulation (GES) outcomes. OBJECTIVE: To measure effects of 72 hours of temporary GES on Gp symptoms. DESIGN, SETTING, AND PATIENTS: From 2005 to 2006, we conducted a hospital-based, randomized, placebo-controlled, crossover trial of two consecutive, 4-day sessions (session 1 and session 2), enrolling 58 patients (11 males, 47 females; mean age 46 years) with GP symptom histories of three etiologies (idiopathic, 38; diabetes mellitus, 13; postsurgical, 7). INTERVENTION: 72 continuous hours temporary GES was provided for group A during session 1, and for group B during session 2. MAIN OUTCOME MEASUREMENTS: Symptoms measured daily; gastric emptying, electrogastrography, and quality of life measured at baseline and session close. RESULTS: In session 1, vomiting decreased in both groups, but was greater with stimulation, resulting in a day 3 difference of -1.02 (95% CI, -1.62 to -0.42; P < .001). Scores did not return to baseline during washout; on day 4, the difference persisted at -1.08 (95% CI, -1.81 to -0.35; P = .005). In session 2, vomiting slightly decreased with stimulation and slightly increased without it; at day 8, the nonactivated group had nonsignificantly greater vomiting, 0.12 (-0.68 to 0.92; P = .762). An overall treatment effect of a slight, nonsignificant daily decrease in average vomiting scores, -0.12 (-0.26 to 0.03; P = .116), was observed by pooling stimulation effects across sessions. LIMITATIONS: Missing data; potential physiological imbalances between groups. CONCLUSIONS: Although overall treatment effects were not significant, differences in favor of stimulation were suggested. Barriers to observing treatment effects included a decrease in vomiting for both groups during session 1, insufficient washout, and the absence of baseline vomiting for some patients. Future studies should better define inclusion criteria, use longer washout periods, randomize by etiology and baseline physiological findings, and pursue alternative designs. ( CLINICAL TRIAL REGISTRATION NUMBER: 00432835.).

Refractory gastroparesis after Roux-en-Y gastric bypass: surgical treatment with implantable pacemaker.

BACKGROUND: Gastroparesis is a rare complication of Roux-en-Y gastric bypass. We evaluate the role of gastric electrical stimulation in medically refractory gastroparesis. METHODS: Patients with refractory gastroparesis after gastric bypass for morbid obesity were studied. After behavioral and anatomic problems were ruled out, the diagnosis of disordered gastric emptying was confirmed by radionuclide gastric emptying. Temporary endoscopic stimulation was used first to assess response before implanting a permanent device. RESULTS: Six patients, all women with mean age of 42 years, were identified. Two patients ultimately had reversal of their surgery with gastro-gastrostomy, while another had a total gastrectomy with persistence of symptoms in all three. Five of the patients evaluated had insertion of a permanent gastric pacemaker, with pacing lead implanted on the gastric pouch (2), the antrum of the reconstructed stomach (1), or the proximal Roux limb (2). Nausea and emesis improved significantly postoperatively; mean total symptom score decreased from 15 to 11 out of 20. There was also a persistent improvement in gastric emptying postoperatively based on radionuclide testing. CONCLUSION: If medical therapy fails, electrical stimulation is a viable option in selected patients with gastroparesis symptoms complicating gastric bypass and should be considered in lieu of reversal surgery or gastrectomy.

Clinical factors associated with unexpected critical care management and prolonged hospitalization after elective cervical spine surgery.

OBJECTIVES: To determine preoperative and operative factors associated with the need for unanticipated critical care management and prolonged hospitalization after cervical spine surgery. DESIGN: Retrospective, case controlled study with data collection over 5 yrs. SETTING: Intensive care unit at a Veterans Affairs hospital. PATIENTS: A total of 109 patients who underwent elective cervical decompression for degenerative disease. INTERVENTIONS: Anterior or posterior cervical spine surgery. MEASUREMENTS AND MAIN RESULTS: Data were recorded with regard to pre- and postoperative neurologic function, extent of surgery, length and cost of hospitalization and critical care, and preoperative co-morbidities. Of 109 patients, 16 (15%) required critical care management in the early postoperative phase (group I). The remainder (n = 93) represented group II. Group I had an average hospital stay of 18.5 days as compared with 6.1 days for group II (p <.001) and a cost difference of approximately $26,000. The incidence of preexisting myelopathy (69%) and the extent of decompression (2.38 levels) were greater in group I than group II (27%, p <.005; 1.67 levels, p <.01). The presence of pulmonary disease (p <.03), hypertension (p <.02), cardiovascular disease (p <.05), and diabetes mellitus (p <.002) all were associated with the need for critical care management and longer hospitalization. CONCLUSIONS: In those patients undergoing decompressive cervical surgery for degenerative disease, the following factors were linked to the need for unanticipated, postoperative critical care and longer hospitalization: multilevel decompression, preexisting myelopathy, pulmonary disease, cardiovascular disease, hypertension, and diabetes mellitus.

BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and beta1 integrin expression in ovarian cancer cells.

Benzoporphyrin derivative monoacid (BPD-MA) photosensitization was examined for its effects on cellular adhesion of a human ovarian cancer cell line, OVCAR 3, to extracellular matrix (ECM) components. Mild BPD-MA photosensitization (approximately 85% cell survival) of OVCAR 3 transiently decreased adhesion to collagen IV, fibronectin, laminin and vitronectin to a greater extent than could be attributed to cell death. The loss in adhesiveness was accompanied by a loss of beta1 integrin-containing focal adhesion plaques (FAPs), although beta1 subunits were still recognized by monoclonal antibody directed against human beta1 subunits. In vivo BPD-MA photosensitization decreased OVCAR 3 adhesiveness as well. Photosensitized adhesion was reduced in the presence of sodium azide and enhanced in deuterium oxide, suggesting mediation by singlet oxygen. Co-localization studies of BPD-MA and Rhodamine 123 showed that the photosensitizer was largely mitochondrial, but also exhibited extramitochondrial, intracellullar, diffuse cytosolic fluorescence. Taken together, these data show that intracellular damage mediated by BPD-PDT remote from the FAP site can affect cellular-ECM interactions and result in loss of FAP formation. This may have an impact on long-term effects of photodynamic therapy. The topic merits further investigation.

Moloney leukemia virus immortalizes B lymphocytes in vitro.

An in vitro culture system in which Moloney murine leukemia virus induces immortalization of mature B lymphocytes has been developed. The cell lines derived in this way are nontumorigenic, and virus production is not required to sustain them. This system provides a new in vitro model with which to study the stepwise process of transformation by retroviruses lacking oncogenes.

Effect of experimentally-prolonged life span on flight performance of houseflies.

Reduction of metabolic rate by the elimination of flying activity extends the life span of male houseflies about two-fold as compared to those permitted to engage in flying activity. Flying performance of flies is known to undergo an age-associated decline. The objective of this study was to determine if such an age-related decline in flight performance is delayed by the reduction of metabolic rate. Flight performance was measured, by cross-sectional sampling at different ages, by the "stationary flight" method, as the total time spent in flight and the number and duration of individual flights and rest stops during a one hour observation period. Flies kept under conditions of low physical activity exhibited a superior flight performance at all ages as compared to those kept under high activity conditions. The decline in flight performance observed in old flies was delayed in the longer-lived low activity flies as compared to the shorter-lived high activity flies. Results support the concept that the rate of aging in houseflies is modified by variations in the level of physical activity.

Isolation of a bacterial host selective for bacteriophage T4 containing cytosine in its DNA.

An Escherichia coli B strain, B834 galU56, has been isolated which supports growth of bacteriophage T4 with cytosine in its DNA while restricting growth of T4 with hydroxymethylcytosine. This host is partially deficient in uridine diphosphoglucose as determined by the ability of DNA isolated from T4 grown on it to accept glucose in an in vitro assay. In this mutant an intact rgl restriction system recognizes unglucosylated hydroxymethylcytosine residues in phage DNA, while the absence of a functional rB restriction function prevents degradation of unmodified DNA containing cytosine.

A model for the packing of cells.

A model is presented for the statistical and geometrical aspects of the packing of cells. The model is closely related to lattice polymer models and the Ising model of ferromagnetism. Fundamental questions of existence and analyticity in the infinite volume limit are discussed, and the results of some initial numerical studies are given.