Determination of ion recombination and polarity effects for the PTW Advanced Markus ionization chamber in synchrotron based scanned proton and carbon ion beams.

The aim of this work was the investigation of the ion recombination and polarity factors (ksat ad kpol) for a PTW Advanced Markus ionization chamber exposed to proton and carbon ion beams at the Centro Nazionale di Adroterapia Oncologica. Measurements with protons were specifically dedicated for ocular treatments, in the low energy range and for small, collimated scanning fields. For both protons and carbon ions, several measurements were performed by delivering a 2D single energy layer of 3x3 cm2 and homogeneous, biologically-optimized SOBPs. Data were collected at different depths in water, by varying the voltage values of the ionization chamber and for two different dose rates (the nominal one and one reduced to 20% of it). The ksat-values were determined from extrapolation of the saturation curves. Furthermore kpol-values were calculated using the recommendations from the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Results showed that the Advanced Markus performs optimally in this clinical scenario characterized by small treatment volumes and high dose gradients although for both particle types, but particularly for carbon ions, a charge multiplication effect up to 1.7% occurs at voltage higher than 150 V. For protons, both the ion recombination and polarity corrections were always smaller than 0.3%, for all the analysed cases and adopted dose rates, so not affecting the dosimetric measurements for clinical routine. For carbon ions the polarity effect can be neglected while ion recombination has to be carefully calculated and cannot be neglected since corrections even higher than 1% can be found, especially at high LET measuring points.

From in vitro research to real life studies: an extensive narrative review of the effects of balneotherapy on human immune response.

PURPOSE: The biologic mechanisms by which balneotherapy (BT) alleviates symptoms of different diseases are still poorly understood. Recently, preclinical models and clinical trials have been developed to study the effects of BT on the immune system. This review summarizes the currently available evidence regarding the effects of spa therapy on the immune response, to confirm the role of BT in the enhancement of immune system and open interesting research fields. METHODS: PubMed and Google Scholar were searched from 1997 up to June 2020, with search criteria including terms related to BT and immune system. We selected only in vitro research, randomized controlled trials (RCTs) or clinical trials. RESULTS: In vitro studies on human and animal samples have demonstrated that thermal waters exert anti-inflammatory and immunomodulatory effects. In particular, H2S donors seem to counteract the inflammatory processes in psoriatic lesions, arthritic fibroblast-like synoviocytes and chondrocytes, and regulate important factors implicated in osteoarthritis pathogenesis and progression. RCTs and clinical trials revealed, after BT, a reduction in circulating levels of pro-inflammatory molecules, such as TNF-α, IL-1ß, and C-reactive protein, and an increase in anti-inflammatory molecules such as the IGF-1 growth factor especially in musculoskeletal diseases. CONCLUSION: Further preclinical studies and RCTs could help to exploit BT in real life for preventive and therapeutic treatments.

Dermatofibrosarcoma protuberans: a tumor in the wide spectrum of the bland-looking spindle cell lesions of the breast.

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor, usually occurring as a cutaneous lesion localized to the trunk or extremities; although it has a high rate of local recurrence, its metastatic potential is very low and complete surgical excision is frequently curative. Most of the cases reported as "DFSP of the breast" are tumors arising in the subcutaneous tissue infiltrating the underlying breast parenchyma. To the best of our knowledge, only 5 cases of DFSP of the breast have been reported to date. We herein present a rare case of DFSP of the breast parenchyma in a 41-year-old female with emphasis on the diagnostic clues and the differential diagnosis with other benign and malignant spindle cell lesions of the breast.

Determination of ion recombination and polarity effect correction factors for a plane-parallel ionization Bragg peak chamber under proton and carbon ion pencil beams.

Within the dosimetric characterization of particle beams, laterally-integrated depth-dose-distributions (IDDs) are measured and provided to the treatment planning system (TPS) for beam modeling or used as a benchmark for Monte Carlo (MC) simulations. The purpose of this work is the evaluation, in terms of ion recombination and polarity effect, of the dosimetric correction to be applied to proton and carbon ion curves as a function of linear energy transfer (LET). LET was calculated with a MC code for selected IDDs. Several regions of Bragg peak (BP) curve were investigated. The charge was measured with the plane-parallel BP-ionization chamber mounted in the Peakfinder as a field detector, by delivering a fixed number of particles at the maximum flux. The dose rate dependence was evaluated for different flux levels. The chamber was connected to an electrometer and exposed to un-scanned pencil beams. For each measurement the chamber was supplied with {±400, +200, +100} V. Recombination and polarity correction factors were then calculated as a function of depth and LET in water. Three energies representative of the clinical range were investigated for both particle types. The corrected IDDs (IDD k s) were then compared against MC. Recombination correction factors were LET and energy dependent, ranging from 1.000 to 1.040 (±0.5%) for carbon ions, while nearly negligible for protons. Moreover, no corrections need to be applied due to polarity effect being <0.5% along the whole IDDs for both particle types. IDD k s showed a better agreement than uncorrected curves when compared to MC, with a reduction of the mean absolute variation from 1.2% to 0.9%. The aforementioned correction factors were estimated and applied along the IDDs, showing an improved agreement against MC. Results confirmed that corrections are not negligible for carbon ions, particularly around the BP region.

Practical approach to diagnosis of bland-looking spindle cell lesions of the breast.

The diagnosis of bland-looking spindle cell lesions of the breast is often challenging because there is a close morphological and immunohistochemical overlap among the different entities. The present review will discuss reactive spindle cell nodule/exuberant scar, nodular fasciitis, inflammatory pseudotumor, myofibroblastoma (classic type), lipomatous myofibroblastoma, palisaded myofibroblastoma, benign fibroblastic spindle cell tumor, spindle cell lipoma, fibroma, leiomyoma, solitary fibrous tumor, myxoma, schwannoma/neurofibroma, desmoid-type fibromatosis, dermatofibrosarcoma protuberans, low-grade fibromatosis-like spindle cell carcinoma, inflammatory myofibroblastic tumor and low-grade myofibroblastic sarcoma arising in the breast parenchyma. The pathologist should be aware of each single lesion to achieve a correct diagnosis to ensure patient a correct prognostic information and therapy. Accordingly representative illustrations and morphological/immunohistochemical diagnostic clues will be provided.

Intestinal-type adenocarcinoma of the vagina: clinico-pathologic features of a common tumor with a rare localization.

Intestinal-type adenocarcinoma is a rare primary vaginal carcinoma and considerably more uncommon than metastatic lesions which represent the most frequent malignancy at this anatomic site. Among all malignant tumors, colorectal, breast and female genital tract carcinomas have the tendency to metastasize to the vagina.As morphologic and immunohistochemical features of intestinal-type adenocarcinoma occurring primarily in the vagina are not specific, clinical and radiologic information is crucial to exclude a metastatic lesion.Herein we present a rare case of intestinal-type adenocarcinoma from a villous adenoma, presenting as a polypoid mass in the posterior wall of vaginal introitus of 51-year-old menopausal woman. To the best of our knowledge, only 19 cases of intestinal-type adenocarcinoma of the vagina have been reported in the English literature so far. Notably the origin from a previous villous adenoma has been well documented only in a few cases.

Perineurioma of the colon: an uncommon tumor with an unusual location. Report of a case and review of the literature.

Perineurioma is a relatively rare benign peripheral nerve sheath tumor composed of cells resembling to normal perineurium. Although this tumor may arise in the context of a nerve (intraneural perineurioma), extraneural perineurioma does occur, frequently involving the soft tissues of the lower and upper extremities, trunk and head and neck. Rarely it has also been reported in visceral organs, including gastrointestinal tract. We herein describe the clinicopathologic features of a rare case of a perineurioma presenting as a polypoid lesion of the sigmoid colon, emphasizing the pathologic diagnostic clues.

Sensitivity study of the microdosimetric kinetic model parameters for carbon ion radiotherapy.

In carbon ion therapy treatment planning, the relative biological effectiveness (RBE) is accounted for by optimization of the RBE-weighted dose (biological dose). The RBE calculation methods currently applied clinically in carbon ion therapy are derived from the microdosimetric kinetic model (MKM) in Japan and the local effect model (LEM) in Europe. The input parameters of these models are based on fit to experimental data subjected to uncertainties. We therefore performed a sensitivity study of the MKM input parameters, i.e. the domain radius (r d ), the nucleus radius (R n ) and the parameters of the linear quadratic (LQ) model (α x and ß). The study was performed with the FLUKA Monte Carlo code, using spread out Bragg peak (SOBP) scenarios in water and a biological dose distribution in a clinical patient case. Comparisons were done between biological doses estimated applying the MKM with parameters based on HSG cells, and with HSG parameters varied separately by ±{5, 25, 50}%. Comparisons were also done between parameter sets from different cell lines (HSG, V79, CHO and T1), as well as versions of the LEM. Of the parameters, r d had the largest impact on the biological dose distribution, especially on the absolute dose values. Increasing this parameter by 25% decreased the biological dose level at the center of a 3 Gy(RBE) SOBP by 14%. Variations in R n only influenced the biological dose distribution towards the particle range, and variations in α x resulted in minor changes in the biological dose, with an increasing impact towards the particle range. ß had the overall smallest influence on the SOBPs, but the impact could become more pronounced if alternative (LET dependent) implementations are used. The resulting percentage change in the SOBPs was generally less than the percentage change in the parameters. The patient case showed similar effects as with the SOBPs in water, and parameter variations had similar impact on the biological dose when using the clinical MKM and the general MKM. The clinical LEM calculated the highest biological doses to both tumor and surrounding healthy tissues, with a median target dose (D 50%) of 40.5 Gy(RBE), while the MKM with HSG and V79 parameters resulted in a D 50% of 34.2 and 36.9 Gy(RBE), respectively. In all, the observed change in biological dose distribution due to parameter variations demonstrates the importance of accurate input parameters when applying the MKM in treatment planning.

A rare case of primary thyroid amyloidosis.

INTRODUCTION: Amyloid goiter is due to the deposition of amyloid in the thyroid, resulting with enlargement of the gland and compressive symptoms. CASE: We herein present a case of a 45-year-old male patient who complained of a big swelling in the neck. Ultrasound showed an enlarged thyroid gland with mediastinal involvement. The multinodular appearance was consistent with the diagnosis of multinodular goiter. He had a history of multiple myeloma but no sign of systemic amyloidosis. DISCUSSION: Thyroid gland was removed and the histopathological examination revealed a diffuse deposition of amyloid associated with metaplastic lipomatosis of the stroma. CONCLUSIONS: The treatment of choice in patients with amyloid goiter is total thyroidectomy to solve compression symptoms.

Calcifying aponeurotic fibroma: a core biopsy-based diagnosis.

Calcifying aponeurotic fibroma (CAF) is a very rare tumor of the extremities, which can be difficult to diagnose due to its wide cyto-architectural pattern. We herein report the clinicopathologic features of a case of CAF localized on the dorsal face of the foot in a 5-year-old male child, diagnosed by needle core biopsy. Differential diagnostic problems are discussed. The present case emphasizes that the diagnosis of CAF can be confidentially rendered on core needle biopsy if the main morphological components of this tumor are concurrently present; however, before making the diagnosis of CAF, the clinical and radiological context should be considered.

Dosimetric characterization of carbon fiber stabilization devices for post-operative particle therapy.

PURPOSE: The aim of this study was to evaluate the dosimetric impact caused by recently introduced carbon fiber reinforced polyetheretherketone (CF/PEEK) stabilization devices, in comparison with conventional titanium (Ti) implants, for post-operative particle therapy (PT). METHODS: As a first step, protons and carbon ions Spread-Out Bragg Peaks (SOBPs) were delivered to CF/PEEK and Ti screws. Transversal dose profiles were acquired with EBT3 films to evaluate beam perturbation. Effects on image quality and reconstruction artifacts were then investigated. CT scans of CF/PEEK and Ti implants were acquired according to our clinical protocol and Hounsfield Unit (HU) mean values were evaluated in three regions of interest. Implants and artifacts were then contoured in the sample CT scans, together with a target volume to simulate a spine tumor. Dose calculation accuracy was assessed by comparing optimized dose distributions with Monte Carlo simulations. In the end, the treatment plans of nine real patients (seven with CF/PEEK and two with Ti stabilization devices) were retrospectively analyzed to evaluate the dosimetric impact potentially occurring if improper management of the spine implant was carried out. RESULTS: As expected, CF/PEEK screw caused a very slight beam perturbation in comparison with Ti ones, leading to a lower degree of dose degradation in case of contouring and/or set-up uncertainties. Furthermore, CF/PEEK devices did not determine appreciable HU artifacts on CT images thus improving image quality and, as a final result, dose calculation accuracy. CONCLUSIONS: CF/PEEK spinal fixation devices resulted dosimetrically more suitable than commonly-used Ti implants for post-operative PT.

Fred: a GPU-accelerated fast-Monte Carlo code for rapid treatment plan recalculation in ion beam therapy.

Ion beam therapy is a rapidly growing technique for tumor radiation therapy. Ions allow for a high dose deposition in the tumor region, while sparing the surrounding healthy tissue. For this reason, the highest possible accuracy in the calculation of dose and its spatial distribution is required in treatment planning. On one hand, commonly used treatment planning software solutions adopt a simplified beam-body interaction model by remapping pre-calculated dose distributions into a 3D water-equivalent representation of the patient morphology. On the other hand, Monte Carlo (MC) simulations, which explicitly take into account all the details in the interaction of particles with human tissues, are considered to be the most reliable tool to address the complexity of mixed field irradiation in a heterogeneous environment. However, full MC calculations are not routinely used in clinical practice because they typically demand substantial computational resources. Therefore MC simulations are usually only used to check treatment plans for a restricted number of difficult cases. The advent of general-purpose programming GPU cards prompted the development of trimmed-down MC-based dose engines which can significantly reduce the time needed to recalculate a treatment plan with respect to standard MC codes in CPU hardware. In this work, we report on the development of fred, a new MC simulation platform for treatment planning in ion beam therapy. The code can transport particles through a 3D voxel grid using a class II MC algorithm. Both primary and secondary particles are tracked and their energy deposition is scored along the trajectory. Effective models for particle-medium interaction have been implemented, balancing accuracy in dose deposition with computational cost. Currently, the most refined module is the transport of proton beams in water: single pencil beam dose-depth distributions obtained with fred agree with those produced by standard MC codes within 1-2% of the Bragg peak in the therapeutic energy range. A comparison with measurements taken at the CNAO treatment center shows that the lateral dose tails are reproduced within 2% in the field size factor test up to 20 cm. The tracing kernel can run on GPU hardware, achieving 10 million primary [Formula: see text] on a single card. This performance allows one to recalculate a proton treatment plan at 1% of the total particles in just a few minutes.

Optimizing the modified microdosimetric kinetic model input parameters for proton and 4He ion beam therapy application.

Models able to predict relative biological effectiveness (RBE) values are necessary for an accurate determination of the biological effect with proton and 4He ion beams. This is particularly important when including RBE calculations in treatment planning studies comparing biologically optimized proton and 4He ion beam plans. In this work, we have tailored the predictions of the modified microdosimetric kinetic model (MKM), which is clinically applied for carbon ion beam therapy in Japan, to reproduce RBE with proton and 4He ion beams. We have tuned the input parameters of the MKM, i.e. the domain and nucleus radii, reproducing an experimental database of initial RBE data for proton and He ion beams. The modified MKM, with the best fit parameters obtained, has been used to reproduce in vitro cell survival data in clinically-relevant scenarios. A satisfactory agreement has been found for the studied cell lines, A549 and RENCA, with the mean absolute survival variation between the data and predictions within 2% and 5% for proton and 4He ion beams, respectively. Moreover, a sensitivity study has been performed varying the domain and nucleus radii and the quadratic parameter of the photon response curve. The promising agreement found in this work for the studied clinical-like scenarios supports the usage of the modified MKM for treatment planning studies in proton and 4He ion beam therapy.

The FLUKA Monte Carlo code coupled with the NIRS approach for clinical dose calculations in carbon ion therapy.

Particle therapy facilities often require Monte Carlo (MC) simulations to overcome intrinsic limitations of analytical treatment planning systems (TPS) related to the description of the mixed radiation field and beam interaction with tissue inhomogeneities. Some of these uncertainties may affect the computation of effective dose distributions; therefore, particle therapy dedicated MC codes should provide both absorbed and biological doses. Two biophysical models are currently applied clinically in particle therapy: the local effect model (LEM) and the microdosimetric kinetic model (MKM). In this paper, we describe the coupling of the NIRS (National Institute for Radiological Sciences, Japan) clinical dose to the FLUKA MC code. We moved from the implementation of the model itself to its application in clinical cases, according to the NIRS approach, where a scaling factor is introduced to rescale the (carbon-equivalent) biological dose to a clinical dose level. A high level of agreement was found with published data by exploring a range of values for the MKM input parameters, while some differences were registered in forward recalculations of NIRS patient plans, mainly attributable to differences with the analytical TPS dose engine (taken as reference) in describing the mixed radiation field (lateral spread and fragmentation). We presented a tool which is being used at the Italian National Center for Oncological Hadrontherapy to support the comparison study between the NIRS clinical dose level and the LEM dose specification.

A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field.

Proton therapy treatment planning systems (TPSs) are based on the assumption of a constant relative biological effectiveness (RBE) of 1.1 without taking into account the found in vitro experimental variations of the RBE as a function of tissue type, linear energy transfer (LET) and dose. The phenomenological RBE models available in literature are based on the dose-averaged LET (LET D ) as an indicator of the physical properties of the proton radiation field. The LET D values are typically calculated taking into account primary and secondary protons, neglecting the biological effect of heavier secondaries. In this work, we have introduced a phenomenological RBE approach which considers the biological effect of primary protons, and of secondary protons, deuterons, tritons (Z = 1) and He fragments (3He and 4He, Z = 2). The calculation framework, coupled with a Monte Carlo (MC) code, has been successfully benchmarked against clonogenic in vitro data measured in this work for two cell lines and then applied to determine biological quantities for spread-out Bragg peaks and a prostate and a head case. The introduced RBE formalism, which depends on the mixed radiation field, the dose and the ratio of the linear-quadratic model parameters for the reference radiation [Formula: see text], predicts, when integrated in an MC code, higher RBE values in comparison to LET D -based parameterizations. This effect is particular enhanced in the entrance channel of the proton field and for low [Formula: see text] tissues. For the prostate and the head case, we found higher RBE-weighted dose values up to about 5% in the entrance channel when including or neglecting the Z = 2 secondaries in the RBE calculation. TPSs able to proper account for the mixed radiation field in proton therapy are thus recommended for an accurate determination of the RBE in the whole treatment field.

Characterization of a commercial scintillation detector for 2-D dosimetry in scanned proton and carbon ion beams.

INTRODUCTION: Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully assessed and periodically checked to guarantee patient safety. This study aimed at characterizing the Lynx® detector (IBA Dosimetry) for commissioning and periodic quality assurance (QA) for proton and carbon ion beams, as compared to EBT3 films, currently used for QA checks. METHODS AND MATERIALS: The Lynx® is a 2-D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. The scintillator was preliminarily characterized in terms of short-term stability, linearity with number of particles, image quality and response dependence on iris setting and beam current; Lynx® was then systematically tested against EBT3 films. The detector response dependence on radiation LET was also assessed. RESULTS: Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements. The strong LET dependence of the scintillator due to quenching effect makes Lynx® suitable only for relative 2-D dosimetry measurements. CONCLUSION: Lynx® appears as a promising tool for commissioning and periodic QA checks for both protons and carbon ion beams. This detector can be used as an alternative of EBT3 films, allowing real-time measurements and analysis, with a significant time sparing.

Biologically optimized helium ion plans: calculation approach and its in vitro validation.

Treatment planning studies on the biological effect of raster-scanned helium ion beams should be performed, together with their experimental verification, before their clinical application at the Heidelberg Ion Beam Therapy Center (HIT). For this purpose, we introduce a novel calculation approach based on integrating data-driven biological models in our Monte Carlo treatment planning (MCTP) tool. Dealing with a mixed radiation field, the biological effect of the primary (4)He ion beams, of the secondary (3)He and (4)He (Z = 2) fragments and of the produced protons, deuterons and tritons (Z = 1) has to be taken into account. A spread-out Bragg peak (SOBP) in water, representative of a clinically-relevant scenario, has been biologically optimized with the MCTP and then delivered at HIT. Predictions of cell survival and RBE for a tumor cell line, characterized by [Formula: see text] Gy, have been successfully compared against measured clonogenic survival data. The mean absolute survival variation ([Formula: see text]) between model predictions and experimental data was 5.3% ± 0.9%. A sensitivity study, i.e. quantifying the variation of the estimations for the studied plan as a function of the applied phenomenological modelling approach, has been performed. The feasibility of a simpler biological modelling based on dose-averaged LET (linear energy transfer) has been tested. Moreover, comparisons with biophysical models such as the local effect model (LEM) and the repair-misrepair-fixation (RMF) model were performed. [Formula: see text] values for the LEM and the RMF model were, respectively, 4.5% ± 0.8% and 5.8% ± 1.1%. The satisfactorily agreement found in this work for the studied SOBP, representative of clinically-relevant scenario, suggests that the introduced approach could be applied for an accurate estimation of the biological effect for helium ion radiotherapy.

Antibacterial activity and immunomodulatory effects on a bovine mammary epithelial cell line exerted by nisin A-producing Lactococcus lactis strains.

Twenty-nine strains of mastitis pathogens were used to study the antibacterial activity of the cell-free supernatants (CFS) of 25 strains of Lactococcus lactis ssp. lactis. Out of the tested strains, only the CFS of L. lactis LL11 and SL153 were active, inhibiting and killing most of the pathogens. By means of ultra-performance liquid chromatography/high resolution mass spectrometry, they were shown to produce nisin A, a class I bacteriocin. A variable sensitivity to nisin A-containing CFS was observed among Streptococcus uberis and Enterococcus faecalis strains. Nonetheless, Streptococcus agalactiae, Strep. uberis, and E. faecalis displayed high minimum inhibitory concentration values, reaching 384 arbitrary units/mL. Interestingly, the minimum inhibitory values and the bactericidal concentrations were almost identical among them for each of the 2 stains, LL11 and SL153. Staphylococci were, on average, less sensitive than streptococci, but the 2 CFS inhibited and killed, at different dilutions, strains of methicillin-resistant Staphylococcus aureus. The immune response to nisin A-containing CFS was tested using the bovine mammary epithelial cell line BME-UV1. Application of CFS did not damage epithelial integrity, as demonstrated by the higher activity of N-acetyl-ß-d-glucosaminidase (NAGase) and lysozyme inside the cells, in both treated and control samples. On the other hand, the increase of released NAGase after 15 to 24h of treatment with LL11 or SL153 live cultures demonstrated an inflammatory response of epithelial cells. Similarly, a significantly higher lysozyme activity was detected in the cells treated with LL11 live culture confirming the stimulation of lysosomal activity. The treatment of epithelial cells with SL153 live culture induced a significant tumor necrosis factor-α downregulation in the cells, but did not influence IL-8 expression. The control of tumor necrosis factor-α release could be an interesting approach to reduce the symptoms linked to clinical intramammary infections. Due to their antibacterial activity and to the stimulation of lysosomal activity of mammary epithelial cells, the L. lactis strains SL153 and LL11 could be of interest for the development of alternative intramammary treatments to control cow mastitis.

Data-driven RBE parameterization for helium ion beams.

Helium ion beams are expected to be available again in the near future for clinical use. A suitable formalism to obtain relative biological effectiveness (RBE) values for treatment planning (TP) studies is needed. In this work we developed a data-driven RBE parameterization based on published in vitro experimental values. The RBE parameterization has been developed within the framework of the linear-quadratic (LQ) model as a function of the helium linear energy transfer (LET), dose and the tissue specific parameter (α/ß)ph of the LQ model for the reference radiation. Analytic expressions are provided, derived from the collected database, describing the RBEα = αHe/αph and Rß = ßHe/ßph ratios as a function of LET. Calculated RBE values at 2 Gy photon dose and at 10% survival (RBE10) are compared with the experimental ones. Pearson's correlation coefficients were, respectively, 0.85 and 0.84 confirming the soundness of the introduced approach. Moreover, due to the lack of experimental data at low LET, clonogenic experiments have been performed irradiating A549 cell line with (α/ß)ph = 5.4 Gy at the entrance of a 56.4 MeV u(-1)He beam at the Heidelberg Ion Beam Therapy Center. The proposed parameterization reproduces the measured cell survival within the experimental uncertainties. A RBE formula, which depends only on dose, LET and (α/ß)ph as input parameters is proposed, allowing a straightforward implementation in a TP system.

Kikuchi-Fujimoto disease: a clinicopathologic update.

Kikuchi-Fujmoto disease (KFD), also known as "histiocytic necrotizing lymphadenitis", is a rare lymphadenitis of unknown origin, but with an excellent prognosis. It is more common in Asia, but isolated cases are also reported in America, Africa and Europe. The disease can have an acute or subacute course, usually develops in 1 to 3 weeks, with spontaneous resolution in 1-4 months. The main clinical sign is cervical lymphadenopathy, especially in the posterior cervical triangle with bulky and painful lymph nodes, usually affecting only one side; rare cases of generalized lymphadenopathy can be seen. This common clinical presentation can also be accompanied by nausea, vomiting, weight loss, weakness, headache and arthralgia. An extranodal extension of the disease, including involvement of skin, eye, and bone marrow localizations, has been rarely described. Most patients have leukopenia or neutropenia with a relative leukocytosis. At an ultrasound exploration of the affected lymph nodes, a hypoechoic aspect can be seen, with an external, thick and irregular hyperechoic ring. As there are no specific tests for KFD, the final diagnosis is histologically-based from lymph node excisional biopsy. Histological examination shows paracortical foci of coagulative necrosis containing karyorrhectic debris, which are surrounded by numerous CD68+/myeloperoxidase (MPO)+ histiocytes, CD68+/CD123+ plasmacytoid dendritic cells, and a minority of small- to large-sized CD8+lymphocytes and immunoblasts. Differential diagnosis mainly includes systemic lupus erithematous (SLE)-related lymphadenopathy and large cell lymphoma. The histological absence of neutrophils, plasmacells, as well as hematoxylin bodies, is a feature which argues against the diagnosis of SLE. In addition, the absence of auto-antibodies and anti-nuclear antibodies is useful in ruling out an autoimmune disorder. Early diagnosis of KFD is crucial to prevent the patients undergo extensive investigations related to suspected malignant lymphomas or other diseases.