Measurements of wavelength dependent scattering and backscattering coefficients by low-coherence spectroscopy

Quantitative measurements of scattering properties are invaluable for optical techniques in medicine. However, noninvasive, quantitative measurements of scattering properties over a large wavelength range remain challenging. We introduce low-coherence spectroscopy as a noninvasive method to locally and simultaneously measure scattering μs and backscattering μb coefficients from 480 to 700 nm with 8 nm spectral resolution. The method is tested on media with varying scattering properties (μs = 1 to 34 mm−1 and μb = 2.10−6 to 2.10−3 mm−1), containing different sized polystyrene spheres. The results are in excellent agreement with Mie theor

Quantitative measurements of absorption spectra in scattering media by low-coherence spectroscopy

Low-coherence spectroscopy (LCS) is a spectroscopic method that allows for quantitative and localized assessment of absorption spectra by combining reflection spectroscopy with low-coherence interferometry. We describe absorption coefficient (µa) measurements by LCS in tissue simulating phantoms with varying scattering and absorbing properties. We used LCS in the 455–680 nm wavelength range with a spectral resolution of 8 nmto obtain µa spectra with ±0.5 mm−1 accuracy. We conclude that LCS is a promising technique for the in vivo determination of tissue chromophore concentrations

A phase I and pharmacokinetic study of intraperitoneal topotecan

Purpose: To evaluate the feasibility and pharmacology of intraperitoneal (IP) topotecan. Patients and methods: Fifteen patients with recurrent ovarian cancer in a phase I trial were treated with escalating IP topotecan doses (5–30 mg/m2) for pharmacokinetic analysis. Results: Dose limiting toxicity (DLT) was acute hypotension, chills and fever at the 30 mg/m2 dose level. Haematological toxicity and abdominal pain were mild for all dose levels studied. Pharmacokinetics: Peak plasma levels of total topotecan were reached at 2.7 ± 1.1 h after IP instillation. The apparent V ss was 69.9 ± 25.4 L/m2, plasma clearance 13.4 ± 2.5 L/h/m2 and plasma T1/2 3.7 ± 1.3 h. The plasma AUC was correlated with the dose (R = 0.95, P < 0.01). The plasma AUC ratio of lactone versus total topotecan (lactone + carboxy-forms) increased with the dose from 16% to 55%, (R = 0.84, P < 0.01). Peritoneal total topotecan was cleared from the peritoneal cavity at 0.4 ± 0.3 L/h.m2 with a T1/2 = 2.7 ± 1.7 h. The mean peritoneal/plasma AUC ratio for total topotecan was 54 ± 34. Conclusion: A substantial dose of topotecan can be delivered by the IP route, achieving cytotoxic plasma levels of topotecan, with acceptable toxicity. The recommended dose for further phase II trials is 20 mg/m2 IP, which enables combination with active doses of other cytotoxic drugs, in view of its limited myelotoxicity when given by this route. © 2001 Cancer Research Campaign http://www.bjcancer.co

3D finite compartment modeling of formation and healing of bruises may identify methods for age determination of bruises

Simulating the spatial and temporal behavior of bruises may identify methods that allow accurate age determination of bruises to assess child abuse. We developed a numerical 3D model to simulate the spatial kinetics of hemoglobin and bilirubin during the formation and healing of bruises. Using this model, we studied how skin thickness, bruise diameter and diffusivities affect the formation and healing of circular symmetric bruises and compared a simulated bruise with a natural inhomogeneous bruise. Healing is faster for smaller bruises in thinner and less dense skin. The simulated and natural bruises showed similar spatial and temporal dynamics. The different spatio-temporal dynamics of hemoglobin and bilirubin allows age determination of model bruises. Combining our model predictions with individual natural bruises may allow optimizing our model parameters. It may particularly identify methods for more accurate age determination than currently possible to aid the assessment of child abuse

How the blood pool properties at onset affect the temporal behavior of simulated bruises

The influence of initial blood pool properties on the temporal behavior of bruises is currently unknown. We addressed this important issue by utilizing three typical classes of bruises in our three-layered finite compartment model. We simulated the effects of their initial shapes, regularity of boundaries and initial blood concentration distributions (gaussian vs. homogeneous) on the hemoglobin and bilirubin areas in the dermal top layer. Age determination of bruises with gaussian hemoglobin concentration was also addressed. We found that the initial blood pool properties strongly affect bruise behavior. We determined the age of a 200-h simulated bruise with gaussian hemoglobin concentration with 3 h uncertainty. In conclusion, bruise behavior depends non-intuitively on the initial blood pool properties; hence, a model that includes shape, area and concentration distribution at onset is indispensable. Future age determination, including inhomogeneous hemoglobin distributions, will likely be based on the presented method for gaussian distributions

Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m−2), doxorubicin (45 mg m−2), cyclophosphamide (600 mg m−2) every 28 days for five cycles, or external RT (45–50 Gy on a 5 days week−1 schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66–1.36; P=0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63–1.23; P=0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited

A tool to balance benefit and harm when deciding about adjuvant therapy

Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary. This study presents a scheme balancing benefit and harm of adjuvant therapy vs no adjuvant therapy. It is illustrated by the available evidence on adjuvant pelvic external beam radiotherapy (RT) for intermediate-risk stage I endometrial carcinoma patients. The scheme comprises five outcome possibilities of adjuvant therapy: patients who benefit from adjuvant therapy (some at the cost of complications) vs those who neither benefit nor contract complications, those who do not benefit but contract severe complications, or those who die. Using absolute risk differences, a fictive cohort of 1000 patients receiving adjuvant RT is categorised. Three large randomised clinical trials were included. Recurrences will be prevented by adjuvant RT in 60 patients, a majority of 908 patients will neither benefit nor suffer severe radiation-induced harm but 28 patients will suffer severe complications due to adjuvant RT and an expected four patients will die. This scheme readily summarises the different possible treatment outcomes and can be of practical value for clinicians and patients in decision making about adjuvant therapies