Definition and estimation of lifetime detriment from radiation exposures: principles and methods.

Although the lifetable methodology is a standard tool in epidemiology and risk assessment, there are a number of differences in the way it has been applied by various advisory committees that have attempted to estimate radiation risks. The most fundamental of these differences concerns the choice of parameter to be estimated: the "excess lifetime risk" is the difference in lifetime risks between exposed and unexposed populations; the "risk of exposure-induced death" is the lifetime risk of dying of a disease attributable to exposure. These two quantities are not the same, even at low doses. Although both quantities have some utility in risk assessment, the "risk of exposure-induced death" comes closer to capturing the total impact of exposure. Other differences between reported risk estimates include details of the calculations, the baseline rates and age distributions of the exposed population, the forms of the models for excess rates, handling of organ-specific doses, and the groupings of cancer sites. These issues are discussed theoretically and illustrated with comparisons of the BEIR V and UNSCEAR reports. Although the risk estimates from these two reports are similar for most cancer sites, it is shown that this happens to be the result of an approximate cancellation of a number of differences that could be quite large.     

II. Vinzenz Czerny (1842–1915): Grand Seigneur of Oncologic Surgery—Life, Influence, and Work of the Second Congress President of the ISS/SIC

Vinzenz Czerny, chairman and professor of surgery in Freiburg im Breisgau and in Heidelberg, Germany, is the typical example of a prominent surgeon with an elegant technique, who was also a keen observer and scientist at the turn of the nineteenth into the early twentieth century. Starting his career in Vienna, Austria, he can be looked upon as the most important disciple of Theodor Billroth. Whereas Billroth may be regarded as the father of modern gastrointestinal surgery, Czerny can be considered the father of modern surgery for intestinal malignancies and multimodal treatment. The early history of visceral cancer therapy is linked with his career. He became a surgeon of the highest rank, with great clinical skill, rare judgment, and vision who contributed essentially to the development of modern surgery. From his early education he maintained a lifelong affection for the natural sciences and was an excellent physiologist and pathologist. During his professional life he successfully built up a well deserved reputation for general and cancer surgery and for the introduction of radio- and chemotherapy into the treatment of tumors. Czerny founded and chaired the first experimental Institute for Cancer Research in Germany. Two years later, in 1908, he presided at the 2nd Congress of the International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC) in Brussels, a congress that was almost entirely devoted to the etiology of visceral cancer and the progress and achievements of its treatment. Czerny left a clear legacy of opinion and methods on which the modern era of surgical cancer treatment is based.     

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.     

Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.

PURPOSE: The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation. EXPERIMENTAL DESIGN: Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy. RESULTS: The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result. CONCLUSIONS: This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy.     

Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography.

PURPOSE: Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m- (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis. PATIENTS AND METHODS: Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices. RESULTS: Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P =.012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered. CONCLUSION: In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.     

Pharmacokinetics and safety of intravitreally delivered etanercept

Background The anti-inflammatory drug etanercept may be an effective therapeutic agent in diabetic retinopathy. In order to further evaluate its potential, the pharmacokinetics and safety of this drug after intravitreal delivery were investigated.Methods After intravitreal administration of etanercept in rabbits, clinical examination, electroretinography (ERG), visually evoked potentials (VEP) and histology were evaluated. The pharmacokinetics and distribution of etanercept were analyzed using fluorescence-coupled protein at 0, 2, 4, and 8 weeks after injection in vitreous, retina, and choroid.Results No adverse effects and signs of toxicity were found. Etanercept showed peak concentrations after 4 weeks in the retina and choroid.Conclusions Intravitreally delivered etanercept is safe and results in high concentrations in the retina and choroid over a long period of time.     

Post-traumatic cervical dystonia: a distinct entity?

BACKGROUND/OBJECTIVE: The incidence of head/neck trauma preceding cervical dystonia (CD) has been reported to be 5-21%. There are few reports comparing the clinical characteristics of patients with and without a history of injury. Our aim was to compare the clinical characteristics of idiopathic CD (CD-I) to those with onset precipitated by trauma (CD-T). METHODS: We evaluated 114 consecutive patients with CD over a 9-month period. All patients were interviewed using a detailed questionnaire and had a neurological examination. Their clinical charts were also reviewed. RESULTS: Fourteen patients (12%) had mild head/neck injury within a year preceding the onset of CD. Between the two groups (CD-I and CD-T), the gender distribution (F:M of 3:2), family history of movement disorders (32% vs. 29%), the prevalence of gestes antagonistes (65% vs. 64%), and response to botulinum toxin were similar. There were non-specific trends, including an earlier age of onset (mean ages 43.3 vs. 37.6), higher prevalence of neck pain (86% vs. 100%), head tremor (67% vs. 79%), and dystonia in other body parts (23% vs. 36%) in CD-T. CONCLUSIONS: CD-I and CD-T are clinically similar. Trauma may be a triggering factor in CD but this was only supported by non-significant trends in its earlier age of onset.     

The auditory midbrain implant: a new auditory prosthesis for neural deafness-concept and device description.

The auditory midbrain implant (AMI) is a new central auditory prosthesis designed for penetrating stimulation of the human inferior colliculus. The major group of candidates for the AMI consists of neurofibromatosis type 2 (NF2) patients who develop neural deafness because of growth and/or surgical removal of bilateral acoustic neuromas. Because of the absence of a viable auditory nerve, these patients cannot benefit from cochlear implants. An alternative solution has been the auditory brainstem implant (ABI), which stimulates the cochlear nucleus. However, speech perception performance in NF2 ABI patients has been limited. The fact that the ABI is able to produce high levels of speech perception in nontumor patients (with inaccessible cochleae or posttraumatic damage to the cochlear nerve) suggests that limitations in ABI performance in NF2 patients may be associated with cochlear nucleus damage caused by the tumors or the tumor removal process. Thus, stimulation of the auditory midbrain proximal to the damaged cochlear nucleus may be a better alternative for hearing restoration in NF2 patients. We propose the central nucleus of the inferior colliculus (ICC) as the potential site. A penetrating electrode array aligned along the well-defined tonotopic gradient of the ICC should selectively activate different frequency regions, which is an important elementfor supporting good speech understanding. The goal of this article is to present the ICC as an alternative site for an auditory implant for NF2 patients and to describe the design of the first human prototype AMI. Practical considerations for implementation of the AMI will also be discussed.