Improved tissue adhesion property of a hydrophobically modified Alaska pollock derived gelatin sheet by UV treatment.

Tissue adhesives have been developed for sealing tissue damaged in surgery. Among these, sheet-type adhesives require a relatively long time to adhere to biological tissue under wet conditions. To address this clinical problem, we fabricated a tissue-adhesive fiber sheet (AdFS) based on decanyl group (C10) modified Alaska pollock-derived gelatin (C10-ApGltn) using electrospinning. Ultraviolet (UV) irradiation of the AdFS was performed to increase the affinity between the AdFS and wet biological tissue by introducing hydrophilic functional groups. The UV irradiated AdFS (UV-C10-AdFS) strongly adhered to porcine pleura within 2 min under wet conditions and showed higher burst strength compared with the original ApGltn (Org-ApGltn) sheet. Hematoxylin-eosin stained sections revealed that a dense UV-C10-AdFS layer remained on the surface of the porcine pleura even after burst strength measurement. Moreover, UV-C10-AdFS has excellent cytocompatibility and efficiently supports the growth of L929 cells. UV-C10-AdFS is a promising adhesive material for sealing wet biological tissue.

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation? : A planning study.

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 S­PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S­PTV to >58 Gy. In the EPI plans, the average median doses to the E­PTV and to the S­PTV 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.

SNP in TXNRD2 associated with radiation-induced fibrosis: a study of genetic variation in reactive oxygen species metabolism and signaling.

PURPOSE: The aim of the study was to identify noninvasive markers of treatment-induced side effects. Reactive oxygen species (ROS) are generated after irradiation, and genetic variation in genes related to ROS metabolism might influence the level of radiation-induced adverse effects (AEs). METHODS AND MATERIALS: 92 breast cancer (BC) survivors previously treated with hypofractionated radiation therapy were assessed for the AEs subcutaneous atrophy and fibrosis, costal fractures, lung fibrosis, pleural thickening, and telangiectasias (median follow-up time 17.1 years). Single-nucleotide polymorphisms (SNPs) in 203 genes were analyzed for association to AE grade. SNPs associated with subcutaneous fibrosis were validated in an independent BC survivor material (n=283). The influence of the studied genetic variation on messenger ribonucleic acid (mRNA) expression level of 18 genes previously associated with fibrosis was assessed in fibroblast cell lines from BC patients. RESULTS: Subcutaneous fibrosis and atrophy had the highest correlation (r=0.76) of all assessed AEs. The nonsynonymous SNP rs1139793 in TXNRD2 was associated with grade of subcutaneous fibrosis, the reference T-allele being more prevalent in the group experiencing severe levels of fibrosis. This was confirmed in another sample cohort of 283 BC survivors, and rs1139793 was found significantly associated with mRNA expression level of TXNRD2 in blood. Genetic variation in 24 ROS-related genes, including EGFR, CENPE, APEX1, and GSTP1, was associated with mRNA expression of 14 genes previously linked to fibrosis (P≤.005). CONCLUSION: Development of subcutaneous fibrosis can be associated with genetic variation in the mitochondrial enzyme TXNRD2, critically involved in removal of ROS, and maintenance of the intracellular redox balance.

MyD88 provides a protective role in long-term radiation-induced lung injury.

PURPOSE: The role of innate immune regulators is investigated in injury sustained from irradiation as in the clinic for cancer treatment or from a nuclear incident. The protective benefits of flagellin signaling through Toll-like receptors (TLR) in an irradiation setting warrant study of a key intracellular adaptor of TLR signaling, namely Myeloid differentiation primary response factor 88 (MyD88). The role of MyD88 in regulating innate immunity and Nuclear factor kappa-B (NF-κB)-activated responses targets this critical factor for influencing injury and recovery as well as maintaining immune homeostasis. MATERIALS AND METHODS: To examine the role of MyD88, we examined immune cells and factors during acute pneumonitic and fibrotic phases in Myd88-deficient animals receiving thoracic gamma (γ)-irradiation. RESULTS: We found that MyD88 supports survival from radiation-induced injury through the regulation of inflammatory factors that aid in recovery from irradiation. The absence of MyD88 resulted in unresolved pulmonary infiltrate and enhanced collagen deposition plus elevated type 2 helper T cell (Th2) cytokines in long-term survivors of irradiation. CONCLUSIONS: These results based only on a gene deletion model suggest that alterations of MyD88-dependent inflammatory processes impact chronic lung injury. Therefore, MyD88 may contribute to attenuating long-term radiation-induced lung injury and protecting against fibrosis.

Contribution of positron emission tomography in pleural disease.

INTRODUCTION: Positron emission tomography (PET) now plays a clear role in oncology, especially in chest tumours. We discuss the value of metabolic imaging in characterising pleural pathology in the light of our own experience and review the literature. BACKGROUND: PET is particularly useful in characterising malignant pleural pathologies and is a factor of prognosis in mesothelioma. Metabolic imaging also provides clinical information for staging lung cancer, in researching the primary tumour in metastatic pleurisy and in monitoring chronic or recurrent pleural pathologies. CONCLUSIONS: PET should therefore be considered as a useful tool in the diagnosis of liquid or solid pleural pathologies.

Pediatric dosimetry for intrapleural lung injections of (32)P chromic phosphate.

Intracavitary injections of (32)P chromic phosphate are used in the therapy of pleuropulmonary blastoma and pulmonary sarcomas in children. The lung dose, however, has never been calculated despite the potential risk of lung toxicity from treatment. In this work the dosimetry has been calculated in target tissue and lung for pediatric phantoms. Pleural cavities were modeled in the Monte Carlo code MCNP within the pediatric MIRD phantoms. Both the depth-dose curves in the pleural lining and into the lung as well as 3D dose distributions were calculated for either homogeneous or inhomogeneous (32)P activity distributions. Dose-volume histograms for the lung tissue and isodose graphs were generated. The results for the 2D depth-dose curve to the pleural lining and tumor around the pleural cavity correspond well with the point kernel model-based recommendations. With a 2 mm thick pleural lining, one-third of the lung parenchyma volume gets a dose more than 30 Gy (V(30)) for 340 MBq (32)P in a 10 year old. This is close to lung tolerance. Younger children will receive a larger dose to the lung when the lung density remains equal to the adult value; the V(30) relative lung volume for a 5 year old is 35% at an activity of 256 MBq and for a 1 year old 165 MBq yields a V(30) of 43%. At higher densities of the lung tissue V(30) stays below 32%. All activities yield a therapeutic dose of at least 225 Gy in the pleural lining. With a more normal pleural lining thickness (0.5 mm instead of 2 mm) the injected activities will have to be reduced by a factor 5 to obtain tolerable lung doses in pediatric patients. Previous dosimetry recommendations for the adult apply well down to lung surface areas of 400 cm(2). Monte Carlo dosimetry quantitates the three-dimensional dose distribution, providing a better insight into the maximum tolerable activity for this therapy.

Radiographic pulmonary and pleural changes after carbon ion irradiation.

PURPOSE: For the treatment of Stage I non-small-cell lung cancers, a Phase I/II study of carbon ion irradiation was undertaken. In the present study, we focus on posttreatment radiographic lung damage: specifically, its timing, features, and relation to dose-volume factors. MATERIALS AND METHODS: Forty-three patients with 44 Stage I non-small-cell lung cancers were treated with carbon ion irradiation ranging from 59.4 to 95.4 photon Gy equivalent dose (GyE) in 18 fractions over 6 weeks, according to our dose escalation protocols. Primary lesions were irradiated by 2-4 portals. Follow-up evaluation with computed tomography (CT) was sequentially performed to assess changes in the lung. CT findings were classified into two categories: pulmonary reaction and pleural reaction. A dose-volume histogram for each patient was calculated, using a three-dimensional CT planning system. Statistical analysis was conducted using Spearman's rank test. RESULTS: The median appearance period of pulmonary reactions was 3 months after the start of carbon ion irradiation, whereas the maximum period was 6 months. The severity of pulmonary reactions statistically correlated with lung volumes irradiated no less than 20 GyE (vol. 20) and 40 GyE (vol. 40) (p = 0.017 and p = 0.0089). Geometrically unique findings in the irradiated fields were observed in 7 patients (16%). The median appearance period of pleural reactions was 4 months after the start of carbon ion irradiation. The occurrence of pleural reactions significantly correlated with planning target volume (p = 0.000098), vol. 20 (p = 0.00011), and vol. 40 (p = 0.00097). CONCLUSIONS: Lung damage after carbon ion irradiation was observed in the parenchyma and in the pleura. The severity of pulmonary reactions was correlated with dose-volume factors. These findings might provide useful information in the planning and management of carbon ion irradiation.

Pleurocutaneous fistula as a complication of radiation treatment in locally advanced breast cancer.

We report the first case of a pleurocutaneous fistula as a consequence of megavoltage radiation therapy for a recurrent locally advanced breast cancer. Several factors, such as previous surgery, blood supply, fraction size, and perhaps increased radiosensitivity, which influence the tolerance of the late reacting normal tissues to radiotherapy, may have predisposed our patient to this rare complication.

In vitro study of ablated lung tissue in Nd:YAG laser irradiation.

BACKGROUND: Neodymium:yttrium-aluminum garnet lasers are used to reduce lung volume. An assessment of the relationship between the histologic and gross findings in the lung irradiated by a laser would be helpful in laser-assisted pneumoplastic procedures. METHODS: In vitro lung lobes surgically resected for pulmonary carcinomas were irradiated with a neodymium:yttrium-aluminum garnet laser at three energy levels in three modes: contact rubbing, contact pointing, and noncontact. Pleural degeneration in 216 samples from 24 lobes was classified as coagulative, amorphous, or destructive. At all energy levels, the laser was applied for 1.5 seconds. RESULTS: Noncontact mode at 7.5 W or 15 W and contact rubbing at 5 W caused coagulative or amorphous degeneration but no destructive degeneration. The energy level correlated with the color of the degenerated pleura. The incidence of destructive pleural degeneration, which led to air leaks as revealed by an air inflation test, was 0% in pink and white samples, 59% in brown samples, and 100% in black samples (p < 0.0001, white versus brown samples). CONCLUSIONS: In neodymium:yttrium-aluminum garnet laser ablation of lung tissue, the color of the degenerated pleura correlates with the intensity of the applied laser energy and the degree of pleural degeneration.

[Morphological examination of the lung tissue ablated with Nd;YAG laser in the treatment of bullous pulmonary disease].

We conducted a morphologic examination of ablated pleurae and bullae to assess the efficacy of Nd;YAG laser irradiation to the lung tissue for the treatment of bullous pulmonary disease. Pleurae and bullae from surgically resected lung tissue to treat pulmonary carcinoma were ablated using a Nd;YAG laser at a power of 10 watts and 1.5 seconds within a 1-centimeter-diameter circle (about 0.2 joule/cm2). Samples were analyzed by light microscopy and scanning electron microscopy. Nd;YAG laser irradiation caused elastic fiber-contraction and gel from collagen both in pleurae irradiated once and in bullae irradiated three times. We conclude that Nd;YAG laser irradiation can be applied to ablate pleurae and bullae into a tight and continuous structure which is important in preventing air leak from the pulmonary parenchyma.

Radiation: an alternative agent for pleurodesis.

Radiotherapy as an alternative agent has been tried for pleurodesis in four proven cases of adenocarcinoma of the lung. This non-invasive technique appears to be beneficial, however, this requires further trials.

[Therapy of pronounced pleural and pericardial effusion in metastatic breast cancer with local mitoxantrone and radiation therapy. Presentation of the intrapleural cytologic findings during this therapy]. / Therapie eines ausgeprägten Pleura- und Perikardergusses bei metastasierendem Mammakarzinom mit lokaler Mitoxantron- und Strahlentherapie. Darstellung des intrapleuralen zytologischen Bildes unter dieser Therapie.

The method of intrapleural Mitoxantrone therapy in case of metastasizing mammary cancer is presented in form of a case report. The uncomplicated procedure, the high rate of remission and the few side effects are the advantages as compared to other methods of pleurodesis. Mitoxantrone could cause an intrapleural inflammatory reaction. That is supported by the cytologic findings before and after the therapy.

Mesothelial papillary proliferation of the pleura associated with radiation therapy: does it have a role in the pathogenesis of mesothelioma?

Diffuse papillary proliferation of mesothelial cells in the pleura mimicking metastatic carcinoma was seen four weeks following radiation therapy for a Pancoast tumor. Such papillary proliferations are not observed incidentally and are envisioned to occur during asbestos-induced carcinogenesis. We postulate that similar papillary lesions may serve as a link in the pathogenesis of radiation-induced mesotheliomas.

Irradiation damage to the lung.

While some degree of injury to normal, non-tumor-bearing, intrathoracic structures always occurs following irradiation for cure or palliation of neoplastic disease, clinical expression of this injury is uncommon. However, under certain circumstances, clinical manifestations may be severe and life threatening. Acute radiographic manifestations of pulmonary injury usually appear either synchronous with or, more typically, seven to ten days after the onset of the clinical syndrome. The acute signs of edema and slight volume loss within the irradiated zone are nonspecific except for their temporal and spatial relationship to the irradiation of the patient. Resolution of the acute changes is followed by pulmonary cicatrization, which is almost always stable within one year after completion of therapy. Change in postirradiation scarring following stabilization of the reaction must always be assumed to be due to some other process. While the radiograph primarily reveals pulmonary injury, all tissues, including the heart and major vessels, are susceptible, and the radiologist must recognize that any change within the thorax of a patient who has undergone thoracic irradiation may be a complication of that treatment. Differentiation of irradiation injury from residual or recurrent tumor, drug reaction, or opportunistic infection may be difficult and at times impossible.