Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma

Background

Successful tumor eradication with photodynamic therapy (PDT) in vivo depends on the optimal combination of treatment parameters. (Low-dose) PDT may additionally induce antitumoral immune responses. Since the naturally occurring hypericin (Hyp) is a promising photosensitizer for PDT, the aim of the study was to investigate phototoxic and immunologic effects of a low-dose Hyp-PDT on murine tumors in contrast to commonly used Hyp-PDT conditions.

Methods

BALB/c mice bearing CT26 colon carcinoma received hypericin intravenously and were irradiated with red light 0.5–4 h later. Tumor development was recorded. Mice were then re-challenged 60 days after the first tumor cell inoculation to investigate an antitumoral immune response.

Results

Different results of tumor/host responses were obtained, ranging from mice exitus over delayed tumor growth to complete tumor regression according to different treatment protocols. PDT with common doses and a 4 h drug–light-interval resulted in a four times delayed tumor growth compared to the control groups. PDT with relatively low doses and a drug–light-interval of 0.5 h led to 100% tumor eradication. Re-challenge of these mice with CT26 mouse colon carcinoma cells prevented new tumor growth.

Conclusions

Not only drug concentrations and light doses seem to determine the efficiency of tumor eradication, but also the localization of hypericin at the time of irradiation. Targets in our low-dose PDT protocol are exclusively the vessels. The advantage of this low-dose PDT beside less drug and light exposure of the animals is reduced skin damage, faster healing of the lesions and induction of an antitumoral immune response.     

Diffusion‐weighted MRI for monitoring tumor response to photodynamic therapy

Purpose:

To examine diffusion‐weighted MRI (DW‐MRI) for assessing the early tumor response to photodynamic therapy (PDT).

Materials and Methods:

Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second‐generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high‐field (9.4 Tesla) small animal MR scanner was used to acquire diffusion‐weighted MR images pre‐PDT and 24 h after the treatment. DW‐MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect.

Results:

Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre‐PDT. The average ADC was 0.511 ± 0.119 × 10^?3 mm²/s pre‐PDT and 0.754 ± 0.181 × 10^?3 mm²/s 24 h after the PDT. There is no significant difference in ADC values pre‐PDT and 24 h after PDT in the control tumors (P = 0.20).

Conclusion:

The change of tumor ADC values measured by DW‐MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4‐PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409–417. © 2010 Wiley‐Liss, Inc.

     

Indocyanine green-based photodynamic therapy with 785nm light emitting diode for oral squamous cancer cells

Background

The efficiency of photodynamic therapy (PDT) used in combination with Indocyanine green (ICG) and the light emitting diode (LED) on oral cancer was evaluated. The safety risk of ICG is known to be very low and ICG has a strong peak in the vicinity of 700–800 nm range which is thought to be a good candidate as a photosensitizer for PDT due to the deep penetration depth into the oral cancer tissue.

Methods

The radiation intensity of homemade LED array was 50 mW/cm² at 0.5 A. To evaluate the maximum efficiency of ICG-PDT on oral cancer, different wavelengths, ICG concentrations, irradiation interval times after administering ICG, and the time durations after PDT were tested. The cytotoxicity was determined by MTT assay, and apoptosis and necrosis were also observed by double staining with SYTO 16 green and PI.

Results

The IC₅₀ value was 10 μM when 785 nm was irradiated, while it was very low in comparison with 630 nm and 895 nm. The values were not very different with varying interval time. The percentage of apoptotic cells increased gradually to 84% at 6 h after 20 μM ICG-PDT and the percentage of necrotic cells dramatically increased to 65% at 3 h after 200 μM ICG-PDT.

Conclusion

Using ICG-PDT with 785 nm LED light, the LED is regarded as a satisfying light source since cancer treatments in the oral region do not require focusing and increased depth of penetration due to longer wavelength enhances treatment effectiveness.     

Porphyrins in urine after administration of 5-aminolevulinic acid as a potential tumor marker

Background

Tumor markers are commonly used for cancer screening and as indicators of therapeutic effects. Certain types of tumor have been known to produce a variety of porphyrins after 5-aminolevulinic acid (ALA) administration. In this study, porphyrins in tumor-bearing mouse urine were analyzed after oral administration of ALA in order to identify new tumor markers excreted in the urine.

Methods

Porphyrin concentrations in the urine of tumor-bearing mice were measured after administration of 1.0 mg of ALA (approximately 50 mg kg⁻¹).

Results

Porphyrin concentrations in the urine of tumor-bearing mice increased after administration of ALA. HPLC analysis of the urine revealed the existence of uroporphyrin (UP) and coproporphyrin (CP) in the urine of ALA-treated tumor-bearing mice. Furthermore, at 3 h after ALA administration, UP concentrations in the urine of tumor-bearing mice significantly increased compared to those in the urine of normal mice.

Conclusion

These results suggest that UP as a precursor of heme detected in the urine of tumor-bearing mice after ALA administration is a potential marker of tumor development.     

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers

Purpose

The purpose of this study is to investigate the dose distribution of proton beam therapy (PBT) using a concomitant boost technique for unresectable pancreatic cancers.

Materials and methods

This simulation study involved 36 patients with unresectable pancreatic cancer. The irradiation dose was set as 67.5 gray equivalent (GyE) with 25 fractions using concomitant boost technique. The irradiation dose was set as 50 GyE to cover the whole target and another posterior beam of 17.5 GyE was added to ensure that 10% isodose line was not delivered to the gastrointestinal (GI) tract. Dose distribution of the gross tumor volume and GI tract was examined.

Results

V_{55GyE, 60GyE, 65GyE} were 80.8, 66.5, and 42.4%, respectively, and mean dose was 64.1 GyE in all patients. The distance from the GI tract showed significant difference in dose distribution (P?=?0.002 in V_55GyE, 0.0009 in V_60GyE, 0.003 in V_65GyE, and 0.02 in mean dose, respectively). Location, tumor diameter, or lymph nodes metastasis did not show any difference.

Conclusions

We found that irradiated dose is closely related to the distance from the GI tract. Clinically, this protocol is expected to have outstanding effects on local control of tumors compared to conventional PBT.

     

Unplanned irradiation of internal mammary lymph nodes in breast cancer

Aims

To evaluate the incidental dose to the internal mammary chain (IMC) in patients treated with three-dimensional conformal radiotherapy, to estimate the predictors affecting the magnitude of IMC receiving dose and to determine the predictive role of clinical parameters on survival.

Materials and methods

Between 2009 and 2015, 348 patients undergoing RT for breast cancer were retrospectively analyzed. All patients underwent our department’s routine procedure for breast cancer. The internal mammary lymph nodes were contoured according to Radiation Therapy Oncology Group (RTOG) concensus. Based on each patient’s dose-volume histograms, the mean doses (D _mean) to internal mammary gland were analyzed. Overall survival and disease-free survival were also evaluated.

Results

The median follow-up time was 38 (range 3–80) months. The D _mean to IMC was 32.8 Gy and the dose delivered to IMC showed a greater coverage in modified radical mastectomy (MRM) group compared with breast conserving surgery (34.6 vs 26.7 Gy). The T-stage of tumor and the N-stage of tumor affected the incidental dose to IMC. The tumor size, the number of involved lymph nodes, the percentage of involved lymph nodes, hormonal status, advanced T-stage and advanced N-stage were the prognostic factors that affect survival.

Conclusion

The IMC received meaningful incidental irradiation dose when treated with two opposite tangential fields and ipsilateral supraclavicular fossa with a single anterior field. The real effect of incidental dose on survival and the hypothesis about the benefit of incidental irradiation of IMC should be examined in clinical studies.

     

Recovery from sublethal damage and potentially lethal damage

Purpose

In order to clarify the biological response of tumor cells to proton beam irradiation, sublethal damage recovery (SLDR) and potentially lethal damage recovery (PLDR) induced after proton beam irradiation at the center of a 10?cm spread-out Bragg peak (SOBP) were compared with those seen after X?ray irradiation.

Methods

Cell survival was determined by a colony assay using EMT6 and human salivary gland tumor (HSG) cells. First, two doses of 4?Gy/GyE (Gray equivalents, GyE) were given at an interfraction interval of 0–6?h. Second, five fractions of 1.6?Gy/GyE were administered at interfraction intervals of 0–5?min. Third, a delayed-plating assay involving cells in plateau-phase cultures was conducted. The cells were plated in plastic dishes immediately or 2–24?h after being irradiated with 8?Gy/GyE of X?rays or proton beams. Furthermore, we investigated the degree of protection from the effects of X?rays or proton beams afforded by the radical scavenger dimethyl sulfoxide to estimate the contribution of the indirect effect of radiation.

Results

In both the first and second experiments, SLDR was more suppressed after proton beam irradiation than after X?ray irradiation. In the third experiment, there was no difference in PLDR between the proton beam and X?ray irradiation conditions. The degree of protection tended to be higher after X?ray irradiation than after proton beam irradiation.

Conclusion

Compared with that seen after X?ray irradiation, SLDR might take place to a lesser extent after proton beam irradiation at the center of a 10?cm SOBP, while the extent of PLDR does not differ significantly between these two conditions.

     

Analysis of computed tomography density of liver before and after amiodarone administration

Purpose

To evaluate CT density of liver changes between before and after amiodarone administration.

Materials and methods

Twenty-five patients underwent non-enhanced CT including the liver before and after amiodarone administration. We set regions of interest (ROIs) at liver S8, spleen, paraspinal muscle, and calculated average CT density in these ROIs, then compared CT density between liver and other organs. Statistical differences between CT density of liver and various ratios before and after administration were determined, along with correlations between cumulative dose of amiodarone and liver density after administration, density change of liver, and various ratios after administration.

Results

Liver density, liver-to-spleen ratio, and liver-to-paraspinal muscle ratio differed significantly between before and after amiodarone administration. No significant correlations were found between cumulative doses of amiodarone and any of liver density after administration, density change of liver, or various ratios after administration.

Conclusion

CT density of liver after amiodarone administration was significantly higher than that before administration. No correlations were identified between cumulative dose of amiodarone and either liver density after administration or density change of liver. Amiodarone usage should be checked when radiologists identify high density of the liver on CT.

     

Evaluation of skin exposure during cerebral CT perfusion studies on a phantom

Objectives

To evaluate the skin dose during cerebral CT perfusion on a phantom, and estimate the weighted CT dose index (CTDIw) to maximum skin dose conversion factors for four types of CT scanners.

Study design

We evaluated the relationship between surface dose during cerebral CT perfusion and distance from the scan center in the x–y plane using a 64-multidetector row CT scanner. Skin doses were also assessed with 4 different 64-multidetector CT scanners.

Results

The surface doses decreased with the distance from the scan center in the x–y plane. The surface doses at the points 6 cm and 10 cm from the scan center in the x–y plane were different from the dose at the point 8 cm by about 15%. CTDIw and skin doses differed among the CT scanners (CTDIw, 143–590 mGy; averaged temporal skin dose, 126–590 mGy). For all the four types of CT scanner, the doses increased in the following order: occipital point < frontal point < temporal points. The ratios of the maximum skin dose (averaged temporal skin dose) to CTDIw differed among the CT scanners (64–100%).

Conclusions

The maximum skin dose during cerebral CT perfusion and the dose to CTDIw ratios differs among CT scanners. The CTDIw is useful for estimation of the maximum skin dose during cerebral CT perfusion using a proper conversion factor specific to each type of CT scanner.     

Contrast ultrasound-guided photothermal therapy using gold nanoshelled microcapsules in breast cancer

Objectives

The purpose of this study was to test whether dual functional gold nano-shelled microcapsules (GNS-MCs) can be used as an ultrasound imaging enhancer and as an optical absorber for photothermal therapy (PTT) in a rodent model of breast cancer.

Methods

GNS-MCs were fabricated with an inner air and outer gold nanoshell spherical structure. Photothermal cytotoxicity of GNS-MCs was tested with BT474 cancer cells in vitro and non-obese diabetes-SCID (NOD/SCID) mice with breast cancer. GNS-MCs were injected into the tumor under ultrasound guidance and treated with near-infrared (NIR) laser irradiation. The photothermal ablative effectiveness of GNS-MCs was evaluated by measuring the surface and internal temperature of the tumor as well as the size of the tumor using histological confirmation.

Results

NIR laser irradiation resulted in significant tumor cell death in GNS-MCs-treated BT474 cells in vitro. GNS-MCs were able to serve as an ultrasound enhancer to guide the intratumoral injection of GNS-MCs and ensure their uniform distribution. In vivo studies revealed that NIR laser irradiation increased the intratumoral temperature to nearly 70 °C for 8 min in GNS-MCs-treated mice. Tumor volumes decreased gradually and tumors were completely ablated in 6 out of 7 mice treated with GNS-MCs and laser irradiation by 17 days after treatment.

Conclusion

This study demonstrates that ultrasound-guided PTT with theranostic GNS-MCs is a promising technique for in situ treatment of breast cancer.     

Stellenwert der Radiochirurgie in der Primärtherapie des Glioblastoma multiforme

Aim

To describe the clinical results and the feasibility of a phase II dose escalation study of small boost target volumes with a radiosurgical technique in patients with positive early postoperative MRI scan.

Patients and Method

Since 1986, 35 patients were treated within a concept for first line therapy. Including criteria were residual tumor ≤5 cm and Karnofsky performance score ≥70. The mean age was 54.5 years. The treatment concept included an operation for reduction of tumor volume and a postoperative irradiation. The postoperative irradiation was divided in 2 parts: first, a hyperfractionated (1.8 Gy single dose twice a day, 54 Gy total dose) irradiation was performed containing the tumor and the edema with a 2 cm safety margin. Secondly, a radiosurgical boost dose was delivered. The target volume of this radiosurgery was the contrast enhancing residual tumor in early postoperative MRI scans. The median boost dose was 15 Gy. Survival curves were calculated according to the Kaplan-Meier method. Quality of life was evaluated using objective criteria such as neurological findings, frequency of seizures and steroid medication

Results

The median survival calculated from the time of diagnosis was 10.1 months. The 1- and 2-year survival rate were 35% and 6%, respectively. Young age tended to longer survival, patients younger than 53 years had a median survival of 10.4 months whereas patients older than 53 years showed a median survival of 9.2 months. The mean value of the boost volume was 22 cm³. Patients with smaller volumes had a median survival of 10.1 months and patients with bigger volumes showed a median survival of 9.9 months. 4.5 months after therapy, 75% of the patients showed improved or stable quality of life.

Conclusion

The feasibility of a radiosurgically delivered boost dose after postoperative irradiation could be demonstrated. The observed survival rate is comparable to the survival rates reported in the literature. Whether or not the radiosur gery after postoperative irradiation is able to prolong survival can only be evaluated in a randomized phase III trial.     

Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis

Purpose

Oral mucositis is a frequent, dose-limiting side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is based on multiple tissue changes, which could offer targets for a biologically tailored treatment. The potential of dermatan sulfate (DS) to modulate radiation-induced oral mucositis was tested in an established preclinical mucositis model.

Methods

Irradiation was either applied alone or in combination with daily DS treatment (4?mg/kg, subcutaneously) over varying time intervals. Irradiation comprised single dose irradiation with graded doses to the lower tongue surface or daily fractionated irradiation of the whole tongue. Fractionation protocols (5?×?3?Gy/week) over one (days 0–4) or two weeks (days 0–4, 7–11) were terminated by an additional local single dose irradiation to a defined treatment field on the lower tongue surface to induce the mucosal radiation response. The additional single dose irradiation (top-up) on day 7 (after one week of fractionation) or day 14 (after 2 weeks of fractionation) comprised graded doses in order to generate full dose–effect curves. Ulceration of the epithelium of the lower tongue, corresponding to confluent mucositis, was analysed as clinically relevant endpoint. Additionally, the time course parameters, latent time and ulcer duration were analysed.

Results

DS treatment significantly reduced the incidence of ulcerations. DS application over longer time intervals resulted in a more pronounced reduction of ulcer frequency, increased latent times and reduced ulcer duration.

Conclusion

DS has a significant mucositis-ameliorating activity with pronounced effects on mucositis frequency as well as on time course parameters.

     

The use of MR imaging to detect residual versus recurrent nasopharyngeal carcinoma following treatment with radiation therapy

Objective

Residual tumor and fibrosis are commonly observed with magnetic resonance (MR) imaging following radiotherapy for nasopharyngeal carcinoma (NPC). Therefore, MR images of NPC following treatment with radiotherapy were retrospectively analyzed to evaluate whether post-radiation changes associated with residual tumors, recurrent tumors, and fibrosis could be distinguished 1 month and 3–6 months after treatment.

Methods

MR images were analyzed for 108 patients who completed radiotherapy for NPC and underwent 5-years of follow-up. The presence and incidence of residual tumor versus fibrosis was evaluated and compared with 5-year tumor recurrence rates.

Results

Residual tumors were detected in 54/108 (50.0%) patients 1 month after radiotherapy, and in 18/108 (16.7%) patients 3–6 months after radiotherapy. Fibrosis was only detected in 59/108 (54.6%) patients 3–6 months after radiotherapy. After 5 years, tumor recurrence occurred in 13/108 (12%) patients, with the average interval between tumor recurrence and the completion of radiotherapy being 29.15 months. In addition, the 1-, 2-, 3-, 4-, and 5-year relapse rates were 1.9%, 5.6%, 9.3%, 11.1%, and 12.0%, respectively. Based on the images analyzed, significant differences in tumor recurrence and residual tumor rate (P = 0.038), and between tumor recurrence and fibrosis (P = 0.021), were observed 1 month and 3–6 months after radiotherapy, respectively.

Conclusions

In this cohort, tumor recurrence was detected 2–3 year after irradiation and a strong correlation between 5-year recurrence rate and detection of residual tumor or fibrosis by MRI up to six months after radiotherapy was observed.     

Hypofractionation with simultaneous integrated boost for early breast cancer

Purpose

To evaluate the feasibility of hypofractionation with SIB in all settings in Germany to prepare a multicenter treatment comparison.

Methods

Eligible patients had histopathologically confirmed breast cancer operated by BCS. Patients received WBI 40.0 Gy in 16 fractions of 2.5 Gy. A SIB with 0.5 Gy per fraction was administered to the tumor bed, thereby giving 48.0 Gy in 16 fractions to the boost-PTV sparing heart, LAD, lung, contralateral breast. The primary study objective was feasibility, administration of specified dose in 16 fractions within 22–29 days with adherence to certain dose constraints (heart; LAD; contralateral breast); secondary endpoints were toxicity, QoL.

Results

151 patients were recruited from 7 institutions between 07/11-10/12. 10 patients met exclusion criteria prior to irradiation. All but two patients (99 %) received the prescribed dose in the PTVs. Adherence to dose constraints and time limits was achieved in 89 % (95 % CI 82 % to 93 %). 11 AE were reported in 10 patients; five related to concurrent endocrine therapy. Two of the AEs were related to radiotherapy: grade 3 hot flushes in two cases. QoL remained unchanged.

Conclusion

Hypofractionation with a SIB is feasible and was well tolerated in this study.

     

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation?

Background

After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation.

Materials and methods

In all, 12 consecutive stage I–IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a “selective” PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an “elective” PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a “selective” pleural irradiation plan (SPI plan) and an “elective” pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]).

Results

In the SPI plans, the average median dose to the S?PTV was 53.6?Gy (range 41–63.6?Gy). In 4 of 12 patients, it was possible to escalate the dose to the S?PTV to >58?Gy. In the EPI plans, the average median doses to the E?PTV and to the S?PTV were 48.6?Gy (range 38.5–58.7) and 49?Gy (range 38.6–59.5?Gy), respectively. No significant dose escalation was achievable.

Conclusion

The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49?Gy to more than 58?Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

     

Differentiation of tumor sensitivity to photodynamic therapy and early evaluation of treatment effect by nuclear medicine techniques

Objective

Our final goal is to develop an appropriate method using nuclear medicine technique for monitoring the effect and prediction of Photodynamic Therapy (PDT) on tumors. The aim of this study is to evaluate the effect of PDT on tumor cells in vitro using ¹⁸F-FDG and ^99mTc-MIBI as tracers.

Methods

Five tumor cell lines (A431, DU145, H1650, LS180, SHIN3) with varied characteristics were irradiated after incubating for 24 h with several doses of Photofrin (PF). Singlet oxygen was monitored by the near-IR emission detection system during irradiation and generated ¹O₂ was calculated. PDT effects were rapidly evaluated by nuclear medicine techniques (uptake of ¹⁸F-FDG and ^99mTc-MIBI) and traditional methods for cell viability (MTT and trypan blue assays) at 3 h after PDT. Intracellular PF concentration was measured by absorption spectrometer and cell protein content was measured by the Lowry method. ¹⁸F-FDG uptake, ^99mTc-MIBI uptake, singlet oxygen, and intracellular PF concentration were standardized by protein content. Decrease % of ¹⁸F-FDG and ^99mTc-MIBI, MTT, and trypan blue was normalized to the control group.

Results

Decrease % of ¹⁸F-FDG was exponentially related to decrease % of MTT (R ² = 0.650, P < 0.01) while decrease % of ^99mTc-MIBI was linearly related to that of MTT (R ² = 0.719, P < 0.01). The decrease % of MTT was more sensitive than that of trypan blue. However, neither ¹O₂ nor PF uptake was correlated with sensitivity to PDT. In addition, ¹⁸F-FDG uptake before PDT was linearly related to decrease % of MTT (R ² = 0.800, P < 0.05).

Conclusions

Our findings in in vitro studies suggest that ^99mTc-MIBI is better than ¹⁸F-FDG for early evaluation of PDT effect, but ¹⁸F-FDG uptake may be used to predict PDT sensitivity before therapy.     

Early Results of Endovenous Ablation with a 980-nm Diode Laser for an Incompetent Vein of Giacomini

Objective

We wanted to evaluate the effectiveness of endovenous ablation of the incompetent vein of Giacomini using a 980-nm diode laser.

Materials and Methods

A total of 18 patients (18 limbs, 4%) had the incompetent vein of Giacomini. Retrograde reflux originating from the great saphenous vein was noted in sixteen limbs and paradoxical diastolic anterograde reflux from the saphenopopliteal junction was observed in two limbs. After tumescent anesthesia, laser ablation using a 980-nm wavelength laser fiber was performed under ultrasound and/or fluoroscopic guidance. Patients were evaluated clinically and with duplex ultrasound at one week and at one, three, six and twelve months after laser ablation for the technical and clinical success.

Results

In the 18 limbs, the technical success rate was 100%. Continued closure of the vein of Giacomini was seen in 18 of 18 limbs after one month, in 12 of 12 limbs after three and six months and in six of six limbs after twelve months. No recanalization of the vein and no major complications occurred.

Conclusion

Endovenous laser ablation with a 980-nm wavelength is an effective and safe procedure for treating an incompetent vein of Giacomini.     

Correlation between dual-phase dynamic multi-detector CT findings and fibrosis within lung adenocarcinoma tumors

Objective

We focused on fibrosis within lung adenocarcinoma tumors in order to retrospectively analyze correlations with dual-phase contrast enhanced dynamic CT findings.

Materials and methods

We evaluated 89 patients with stage I lung adenocarcinoma who underwent dynamic CT scans (80–96 mL of contrast material, 2.5–3 mL/s injection) and tumor resections. Attenuation values of both the early phase (21–37 s after injection) and the delay phase (91–95 s) of enhanced CT minus the baseline plain CT attenuation were calculated as ΔEarly and ΔDelay. An early enhancement ratio was defined as ΔEarly/ΔDelay × 100. These enhancement patterns were compared with patient and tumor characteristics, including scar grades that were the degrees of fibrosis within tumors evaluated semi-quantitatively by pathologists.

Results

From multivariate analysis, only the tumor scar grade showed significant correlations with ΔEarly (p < 0.001) and the early enhancement ratio (p < 0.001). For ΔEarly and the early enhancement ratio, there were significant differences among 4 groups based on tumor scar grades (p = 0.003 and p = 0.006, respectively); a higher scar grade tumor tended to show lower enhancement at the early phase.

Conclusions

There was a significant negative correlation between the amount of fibrosis and the enhancement grade at the early phase of contrast enhanced dynamic CT in stage I lung adenocarcinoma. Dynamic CT findings could be modified by the degree of fibrosis within a lung tumor.     

In vitro photodynamic inactivation of Candida spp. by different doses of low power laser light

This study evaluated the efficacy of PDT in photoinactivation of Candida species using methylene blue (MB) and irradiation with a diode laser (660 nm, 40 mW). Suspensions of Candida species were obtained containing 10⁶ cfu/ml, transferred to 96-holes plates and exposed to 03 doses of laser light (60 J/cm², 120 J/cm², 180 J/cm²) in the presence of MB. Additional suspensions were treated with only the MB, the laser light or with 0.85% saline (control groups). After the treatments, 1 μl aliquot of the suspensions was plated in duplicate on SDA. The plates were incubated at 37 °C for 24–48 h and after this period there was the counting of colonies (cfu/ml). The three evaluated doses determined meaningful inactivation of Candida spp. (p < 0.05). The 180 J/cm² dose was the most effective, inactivating 78% of cfu/ml. At a dose of 180 J/cm²C. albicans was the most susceptible specie. PDT has demonstrated effectiveness in the inactivation of Candida spp.     

Long-term results after 12-year follow-up of patients treated with whole-breast and boost irradiation after breast-conserving surgery

Purpose

The long-term outcomes of whole-breast and boost irradiation after breast-conserving surgery (BCS) for patients with breast cancer were retrospectively analyzed.

Materials and methods

Patients who received whole-breast and boost irradiation after BCS from 1990 to 2002 were included. Boost irradiation was administered to each tumor bed, regardless of the surgical margin status. The median doses of whole-breast and boost irradiation were 45 Gy in 25 fractions (range 36–45 Gy), and 14 Gy in 7 fractions (range 0–14 Gy), respectively.

Results

Data for 306 patients were analyzed. With a median follow-up time of 144 months, the 10-year overall survival, disease-free survival, ipsilateral breast tumor recurrence (IBTR), and metachronous contralateral breast cancer (MCBC) occurrence rates were 93.0, 84.1, 2.1, and 4.1 %, respectively. In the multivariate analysis, pT2 was a significant risk factor for IBTR (p = 0.041), while age ≤ 50 years and pT2 were significant risk factors for MCBC occurrence (p = 0.003 and 0.043, respectively). One patient (0.3 %) developed angiosarcoma in the irradiated region 120 months after the completion of radiation therapy.

Conclusion

The 12-year outcome of breast-conserving therapy using whole-breast and boost irradiation with doses of 45 and 14 Gy, respectively, was favorable.