The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.     

Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

The aim of the study was to investigate whether hypothermic oxygenated liver perfusion after cold liver preservation resuscitated metabolic parameters and whether this treatment had a benefit for liver viability upon reperfusion.
We preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3 h (oxygenated modified UW) after 10 h cold storage. We assessed viability of livers after preservation and after ischemic rewarming + normothermic reperfusion ex vivo . Ten hour cold storage reduced mitochondrial cytochrome oxidase and metabolically depleted the livers. Oxygenated perfusion after cold storage resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome oxidase. Reperfusion after 10 h cold storage increased formation of superoxid anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10 h cold storage + 3 h hypothermic oxygenated perfusion resulted in no changes of lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and of caspase activation, as compared to fresh resected livers.
This study demonstrates, that a metabolically depleted liver due to cold storage can be energy recharged by short-termed cold machine perfusion. The machine perfused graft exhibited improved viability and functional integrity.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response.

PURPOSETo evaluate the hemodynamics and tissue response associated with stent placement in low-flow-velocity arteries.METHODSSix self-expanding nitinol stents (5.5 mm caliber) were implanted transfemorally within the proximal segments of vertebral arteries (2.5 mm diameter) in six adult dogs during anticoagulative protection.RESULTSControl angiograms demonstrated patency and 20% dilatation of all stented arteries. One artery was partially thrombosed 1 week later and subsequently showed a 50% stenosis. Throughout the observation period (4 to 9 months after stenting), the other five arteries remained patent without significant narrowing (< or = 15%). Small cervical muscle branches originating from the vertebral arteries within the stented segments remained patent. No major branch occlusions of the vertebrobasilar system were detected. Stent migration or kinking did not occur. MR studies of the brain 4 months after implantation revealed no infarcted areas. These findings were confirmed with brain sections. Stented artery specimens showed delayed stent dilatation. A comparison of the total mean thickness of intima covering the five 30- to 40-mm stents removed at 4, 6, and 9 months showed no significant difference (338, 332, and 389 microns, respectively). Histologic findings verified the macroscopic impression of a thicker intima at the inner curve of the stented artery segments and at the junctions of the stent filaments. The shortest (10 mm) stent had the thinnest neointimal growth (155 microns). Stented vessels showed compression of the media with atrophy, but without necrosis or perforation. Scanning electron photomicrographs revealed intact endothelial cell linings with typical elongated cells.CONCLUSIONSNo significant risk of thromboembolic events exists after implanting these nitinol stents in nonatherosclerotic vertebral arteries in dogs. Thicker neointimal growth after stenting may result from either low wall shear stress with possible flow separation or from changes in the shape and size of the stent, or both.     

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Effects of diltiazem in acute and long-term administration

In 16 patients with unstable angina pectoris haemodynamic and clinical effects of diltiazem were investigated. In a second group patients (n = 11) with unstable or therapy-refractory course the long-term effect was tested. The acute intervention with injected and infused diltiazem via an improved oxygen balance due to decreased minute work and reduced product of cardiac frequency and pressure stabilized the clinical picture from the haemodynamic aspect. The decreases of the ST segment were significantly lower. In the long-term use a significant influence on the frequency of angina pectoris with increase of the range of efficacy by one NYHA-state was the result. Diltiazem can be regarded as alternative medicament in unstable phases and in therapy-refractory courses of the chronic coronary heart disease.     

Grenzen und Möglichkeiten der Glaskörperchirurgie bei diabetischer Retinopathie

Hintergrund: Verschiedene Indikationen für glask?rperchirurgische Eingriffe bei Komplikationen der diabetischen Retinopathie haben sich etabliert. Jedoch gibt es wenig Daten zu der Frage, in welchen Situationen auf einen Eingriff wegen aussichtsloser funktioneller Prognose verzichtet werden sollte. Material und Methode: Die Krankengeschichten von 389 Patienten, die zwischen 1990 und 1994 in unserer Klinik wegen Komplikationen der diabetischen Retinopathie vitrektomiert worden sind, wurden retrospektiv analysiert. Die Nachbeobachtung betrug mindestens 6 Monate, im Median 26 Monate. Mit multivariaten, logistischen Regressionsanalysen wurden Faktoren ermittelt, die mit schlechten postoperativen, funktionellen Ergebnissen korrelieren. Ein mathematisches Modell wurde entwickelt, welches die Einsch?tzung der Prognose für verschiedene Ausgangssituationen erlaubt. Ergebnisse: Bei 45 Augen (12%) stieg der postoperative Visus nicht über 1/50. Risikofaktoren waren Ablatio der Makula, Ausdehnung der Ablatio, Rubeosis und Dauer der Visusminderung. ?hnliche Risikofaktoren gelten auch für Revisionsoperationen. Bei einem Auge mit totaler Traktionsablatio von über 6 Monaten Dauer und Rubeosis liegt die berechnete Wahrscheinlichkeit für einen postoperativen Visus über 1/50 lediglich bei 2%. Schlu?folgerungen: Bei totaler Traktionsablatio, insbesondere bei Rubeosis und l?ngerem Bestehen der Ablatio, ist die Prognose extrem schlecht. Auf operative Ma?nahmen sollte hier verzichtet werden.