Intercomparison of Monte Carlo calculated dose enhancement ratios for gold nanoparticles irradiated by X-rays: Assessing the uncertainty and correct methodology for extended beams.

Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in the order of several tens of micrometers from the GNP surface. As it has come to our attention that the figures in our paper have given rise to misinterpretation as showing 'the' DERs of GNPs under diagnostic X-ray irradiation, this article presents estimates of the DERs that would have been obtained with realistic radiation field extensions and presence of secondary particle equilibrium (SPE). These DER values are much smaller than those for a narrow-beam irradiation shown in our paper, and significant dose enhancement is only found within a few hundred nanometers around the GNP. The approach used to obtain these estimates required the development of a methodology to identify and, where possible, correct results from simulations whose implementation deviated from the initial exercise definition. Based on this methodology, literature on Monte Carlo simulated DERs has been critically assessed.

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes.

PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.

Femtosecond dark-field imaging with an X-ray free electron laser.

The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.

Laser-assisted resection of a giant pulmonary chondrohamartoma--a case report.

A rare case of a giant pulmonary chondromatous hamartoma (15 cm, 1350 g) resected by a new laser system (Nd:YAG, 1318 nm, 40 W) is presented. The laser management of a hamartoma resection--the largest reported to date in the literature--is presented here.

Surgical treatment of hepatic and pulmonary metastases from non-colorectal and non-neuroendocrine carcinoma.

BACKGROUND: Surgical resection is standard treatment for colorectal and neuroendocrine liver metases provided the tumor can be removed completely. The same is true for isolated pulmonary metastases. To date, only few reports have addressed the value of surgical resection of organ metastases from other solid tumors. METHODS: The literature was searched by Medline, conference proceedings and cross-referencing of published articles for information pertaining to the long-term results of surgical treatment of non-colorectal and non-neuroendocrine (NCNN) liver or lung metastases. RESULTS: Resection of hepatic and pulmonary metastases is increasingly performed in non-colorectal and non-neuroendocrine malignancies. Mortality and morbidity of hepatic and pulmonary resection are low and 5 year survival can be expected to reach some 20-30 percent, irrespective of the histological type of the primary tumor. CONCLUSION: Resection of hepatic or pulmonary metastasis should be considered in all patients with low operative risk provided that complete resection is possible.

Surgical therapy for loco-regional recurrence and distant metastasis of gastric cancer.

The appearence of distant metastases or local recurrence is assumed to render gastric cancer incurable. However, experience with colorectal cancer has shown that patients with recurrent disease may have a chance for cure, if recurrent or metastatic disease can be completely resected. Since improved imaging allows detection of ever smaller tumour deposits, we have reviewed the pertinent literature to determine the current surgical options for recurrent or metastatic gastric cancer. Metastatic disease or local recurrence is rarely resectable. Tumour recurrence in the remnant stomach after partial gastrectomy can be treated by secondary total gastrectomy and may occasionally result in long-term survival. Other types of local recurrence are generally not amenable to complete resection. The same is true for distant metastases. If, however, distant metasases are technically resectable, 5 year survival of approximately 20% has been documented. Solitary and late appearing metachronous tumours are associated with an improved prognosis. As a consequence resection of distant metastases should be considered, because the risk of metastasectomy is generally low and there is no alternative treatment with a chance for cure.

Impact of diagnostic laparoscopy on the management of gastric cancer: prospective study of 120 consecutive patients with primary gastric adenocarcinoma.

BACKGROUND: Peritoneal seeding or liver metastases found at laparotomy usually preclude curative treatment in patients with gastric adenocarcinoma. Such exploratory laparotomies may be avoided by diagnostic laparoscopy. However, routine diagnostic laparoscopy does not benefit those patients who proceed to laparotomy after negative laparoscopy. The aim of this study was to evaluate prospectively the selective use of laparoscopy in uncertain situations. METHODS: One hundred and twenty consecutive patients with primary gastric adenocarcinoma were studied prospectively. Diagnostic laparoscopy was performed in patients with clinical T4 tumours or suspected metastases, unless laparotomy was required for symptomatic disease. RESULTS: Ninety-six of 120 patients were selected for immediate laparotomy with curative intent (n = 81) or for palliation (n = 15). In two of the 81 patients gastrectomy was abandoned because of unexpected peritoneal carcinomatosis. Fifteen patients underwent diagnostic laparoscopy, which identified intra-abdominal metastases in six; the other nine patients proceeded to laparotomy, which revealed peritoneal metastases not detected at laparoscopy in four patients. The remaining nine patients had overt metastases and were referred for systemic chemotherapy without abdominal exploration. CONCLUSION: Diagnostic laparoscopy in selected patients effectively limits the number of unnecessary invasive staging procedures. Routine use of diagnostic laparoscopy in all patients with gastric adenocarcinoma is not warranted.

Intussusception of the appendix secondary to mucinous cystadenoma.

Intussusception of the appendix vermiformis in adults is an unusual entity. We present a 52-year-old male patient with intussusception of the appendix due to a mucinous cystadenoma, and discuss the clinical features, preoperative diagnosis, classification and therapy of this condition together with a review of the literature.

[Long-term quality of life after continence-preserving proctocolectomy for ulcerative colitis and familial adenomatous polyposis]. / Lebensqualität im Langzeitverlauf nach kontinenzerhaltender Proktocolektomie wegen Colitis ulcerosa und familiärer adenomatöser Polyposis.

After ileal pouch-anal anastomosis in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP), quality of life is a relevant factor for the assessment of the operation's success, in addition to postoperative morbidity and functional outcome. Between 1982 and 1995 restorative proctocolectomy was performed in 453 patients (UC: n = 332; FAP: n = 121) at the Department of Surgery, University of Heidelberg. We studied postoperative quality of life through a long-term follow-up study (median follow-up time 43.2 months). This study 1 year or more following ileostomy closure of persons who had undergone J-pouch anastomosis (n = 243 total; UC n = 185, FAP n = 58) revealed that at the time of follow-up, the underlying disease (UC versus FAP) and successfully treated complications are without influence on the quality of life. The patient's age (P < 0.01) and the presence of unsuccessfully treated complications (P < 0.0001) showed a significant influence on the quality of life. There was a distinct relation between the functional index and the quality of life index (coefficient of correlation r = -0.714). However, quality of life, comparable to that of healthy controls, can be achieved with UC and FAP patients by restorative proctocolectomy only if postoperative complications can be avoided or are successfully treated.