Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren''s disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children.     

Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres.

Treatment for nonresectable hepatocellular carcinoma (HCC) is palliative. The relatively greater arteriolar density of hepatic tumors compared with normal liver suggests that intrahepatic arterial administration of 90Y-microspheres can be selectively deposited in tumor nodules and results in significantly greater radiation exposure to the tumor than external irradiation. The purpose of this study was to determine the proportion (frequency) and duration of response, survival, and toxicity after intrahepatic arterial injection of 90Y-microspheres in patients with HCC. METHODS: Patients with documented HCC, Eastern Cooperative Oncology Group performance status 0-3, adequate bone marrow, and hepatic and pulmonary function were eligible for study. Patients who had significant shunting of blood to the lungs or gastrointestinal (GI) tract or who could not undergo cannulation of the hepatic artery were excluded. Patients received a planned dose of 100 Gy through a catheter placed into the hepatic artery. RESULTS: Twenty-two patients were treated with 90Y-microspheres; 20 of the treated patients (median age, 62.5 y) were evaluated for treatment efficacy. Nine patients were Okuda stage I, and 11 were Okuda stage II. The median dose delivered was 104 Gy (range, 46-145 Gy). All 22 treated patients experienced at least 1 adverse event. Of the 31 (15%) serious adverse events, the most common were elevations in liver enzymes and bilirubin and upper GI ulceration. The response rate was 20%. The median duration of response was 127 wk; the median survival was 54 wk. Multivariable analysis suggested that a dose >104 Gy (P = 0.06), tumor-to-liver activity uptake ratio >2 (P = 0.06), and Okuda stage I (P = 0.07) were associated with longer survival. CONCLUSION: Significantly higher doses of radiation can be delivered to a HCC tumor by intrahepatic arterial administration of 90Y-microspheres than by external beam radiation. This treatment appears to be beneficial in nonresectable HCC with acceptable toxicity.     

Nitrous oxide anxiolysis for elective cesarean section

STUDY OBJECTIVE: To determine if inhaled 40% nitrous oxide (N(2)O) via facemask is an effective anxiolytic in women undergoing elective cesarean section under spinal anesthesia. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Tertiary-care women's hospital. PATIENTS: Sixty American Society of Anesthesiologists physical status I and II patients scheduled for elective cesarean section under spinal anesthesia. INTERVENTIONS: Patients were randomized to 2 groups to receive either 100% O2 via facemask or 40% N2O in O2 via facemask. MEASUREMENTS: Vital signs (blood pressure, heart rate, and oxygen saturation) and measured variables (visual analog scale [VAS] anxiety, VAS pain, and sedation scores) were obtained at specific periods during the procedure (preoperatively, entering the operating room, spinal injection, skin incision, uterine incision, delivery, and at the conclusion of the surgical procedure). In addition, surgical time and delivery time, mean dose and percentage of patients requiring ephedrine or phenylephrine boluses, the emesis rate, and Apgar scores were measured. MAIN RESULTS: No differences were noted with respect to maternal mean blood pressure, heart rate, pulse-oximeter oxygen saturation, and sedation or VAS pain scores during the measured periods. No differences were noted in surgical and delivery times, mean dose, or percentage of patients who required ephedrine or phenylephrine to maintain maternal blood pressure, the emesis rate, or 1- and 5-minute Apgar scores. Mean anxiety scores for the N2O group were significantly lower at the time of spinal injection, skin incision, and uterine incision. Multivariate analysis of variance for high-anxiety patients (> or =50 VAS) revealed significantly lower VAS scores in the N2O group, compared with the O2 group again at spinal injection, skin incision, and uterine incision. CONCLUSIONS: Inhaled 40% N2O via facemask provides effective anxiolysis in women undergoing elective cesarean section under spinal anesthesia in patients with high anxiety (> or =50 VAS) at the time of spinal injection, skin incision, and uterine incision.     

Ciliated hepatic foregut cyst in a young child

Ciliated hepatic foregut cysts are a rare entity usually found in adults. We present a case of a 3-year-old boy incidentally noted to have a radiographically complex liver cyst on computed tomographic scan. Given the complex appearance, the cyst was excised. Pathology revealed a ciliated hepatic foregut cyst. This is the second child and youngest patient affected with this lesion reported in the literature. The etiology of the lesion and an argument for surgical removal in pediatric patients are presented.     

Restoration of liver mass after partial hepatectomy--implications for living donor liver transplantation

In living donor liver transplantation, the recipient liver undergoes more rapid regeneration than the remnant liver in the donor. In this study we investigated the factors which may be responsible for the difference in the regenerative response between the donor and the recipient. Long Evans rats were subjected to either partial hepatectomy (PH) or sham operation (SH) and were treated with liver cytosol (C) and cyclosporine (Cy). The rats were sacrificed at 24, 48, 72 and 96 hours and 1 and 2 weeks postoperatively. The livers were removed to determine the liver weight/body weight (LW/BW) ratio and the mitotic index. The mitotic index, serum aspartate transferase (AST) and serum alanine transferase (ALT), although unchanged in the SH groups, were increased in the rats treated with PH + C + Cy, and were greater than after PH only. However LW/BW ratios increased after PH but had returned to preoperative levels by 2 weeks. The changes in LW/BW ratio were not modified by the cytosol or cyclosporine.     

Dermatologic Surgical Research and the Institutional Review Board

BACKGROUND: Dermatologic surgical techniques have transformed cosmetic surgery over the last two decades. Many of the advances in cutaneous laser surgery, botulinum toxin injections, tumescent liposuction, and the latest filler agents have been evaluated on willing volunteers as part of organized trials under the auspices of an Institutional Review Board (IRB). OBJECTIVES: To review the developmental history of today's IRB and to provide relevance to cosmetic dermatologic research. RESULTS: Although an IRB must evaluate the "voluntariness" of a proposed research protocol, the risk-benefit ratio, particularly of elective cosmetic dermatologic surgical human studies, is of even greater importance. CONCLUSION: As more dermatologic surgeons become involved in clinical research, an understanding of the function and purpose of the IRB has become increasingly important. Research relating to cosmetic dermatologic procedures raises challenging and perplexing problems for an IRB.     

Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions

Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.     

Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways

Hyperinsulinism of infancy (HI) is a congenital defect in the regulated release of insulin from pancreatic beta-cells. Here we describe stimulus-secretion coupling mechanisms in beta-cells and intact islets of Langerhans isolated from three patients with a novel SUR1 gene defect. 2154+3 A to G SUR1 (GenBank accession number L78207) is the first report of familial HI among nonconsanguineous Caucasians identified in the U.K. Using patch-clamp methodologies, we have shown that this mutation is associated with both a decrease in the number of operational ATP-sensitive K+ channels (KATP channels) in beta-cells and impaired ADP-dependent regulation. There were no apparent defects in the regulation of Ca2+- and voltage-gated K+ channels or delayed rectifier K+ channels. Intact HI beta-cells were spontaneously electrically active and generating Ca2+ action currents that were largely insensitive to diazoxide and somatostatin. As a consequence, when intact HI islets were challenged with glucose and tolbutamide, there was no rise in intracellular free calcium ion concentration ([Ca2+]i) over basal values. Capacitance measurements used to monitor exocytosis in control and HI beta-cells revealed that there were no defects in Ca2+-dependent exocytotic events. Finally, insulin release studies documented that whereas tolbutamide failed to cause insulin secretion as a consequence of impaired [Ca2+]i signaling, glucose readily promoted insulin release. Glucose was also found to augment the actions of protein kinase C- and protein kinase A-dependent agonists in the absence of extracellular Ca2+. These findings document the relationship between SUR1 gene defects and insulin secretion in vivo and in vitro and describe for the first time KATP channel-independent pathways of regulated insulin secretion in diseased human beta-cells.     

Bioabsorbable versus stainless steel screw fixation of the syndesmosis in pronation-lateral rotation ankle fractures: a prospective randomized trial

Thirty-two patients who had pronation-lateral rotation (PLR) fractures occurring four centimeters or more proximal to the ankle joint or lower if the talus was displaced greater than one centimeter laterally were enrolled in this study. Seventeen patients were randomized to fibular plate fixation with a 4.5 ml polylactic acid (PLA) bioabsorbable syndesmotic screw, and fifteen patients randomized to fibular plate fixation with a 4.5 mm stainless steel syndesmotic screw. All thirty-two patients had uncomplicated healing of their fibular fracture without loss of reduction. There was neither evidence of osteolysis nor sterile effusion in the patients who were treated with the PLA screw. There were no wound complications in either group. No difference in range of motion or subjective complaints was noted in either group. Use of the PLA syndesmotic screw at short-term follow-up was well tolerated and avoided the need for subsequent screw removal.