Surgical outcomes of video-assisted neck surgery for papillary thyroid carcinoma.

PURPOSE: New approaches to endoscopic thyroid surgery have been developed to improve cosmetic results, one of which is video-assisted neck surgery (VANS). The present study investigates the safety and effectiveness of thyroidectomy by VANS as oncologic surgery for papillary thyroid carcinoma (PTC). METHODS: The subjects of this retrospective study were 121 patients with PTC, who underwent hemi-thyroid lobectomy and central lymph node dissection via open surgery (n = 102) or VANS (n = 19) at Tokushima University Hospital between 2011 and 2023. We performed 1:1 propensity score matching and then compared the surgical outcomes between the two matched groups. RESULTS: Propensity score matching generated 18 distinct examination pairs. The VANS group had significantly less blood loss (P = 0.003), but a longer operative time (P < 0.001) than the open thyroidectomy group. There were two cases of transient recurrent laryngeal nerve paralysis and one case of recurrence in the lateral regional lymph nodes in the VANS group. However, no significant differences were observed in the incidence of complications (P = 0.243) or recurrence (P = 0.500) between the two groups. CONCLUSION: VANS is a safe and effective surgical procedure for PTC, but longer follow-up is needed to assess tumor recurrence.

A new predictive parameter for dose-volume metrics in intensity-modulated radiation therapy planning for prostate cancer: Initial phantom study.

BACKGROUND: Organ-at-risk (OAR) sparing is often assessed using an overlap volume-based parameter, defined as the ratio of the volume of OAR that overlaps the planning target volume (PTV) to the whole OAR volume. However, this conventional overlap-based predictive parameter (COPP) does not consider the volume relationship between the PTV and OAR. PURPOSE: We propose a new overlap-based predictive parameter that consider the PTV volume. The effectiveness of proposed overlap-based predictive parameter (POPP) is evaluated compared with COPP. METHODS: We defined as POPP = (overlap volume between OAR and PTV/OAR volume) × (PTV volume/OAR volume). We generated intensity modulated radiation therapy (IMRT) based on step and shoot technique, and volumetric modulated arc therapy (VMAT) plans with the Auto-Planning module of Pinnacle3 treatment planning system (v14.0, Philips Medical Systems, Fitchburg, WI) using the American Association of Physicists in Medicine Task Group (TG119) prostate phantom. The relationship between the position and size of the prostate phantom was systematically modified to simulate various geometric arrangements. The correlation between overlap-based predictive parameters (COPP and POPP) and dose-volume metrics (mean dose, V70Gy, V60Gy, and V37.5 Gy for rectum and bladder) was investigated using linear regression analysis. RESULTS: Our results indicated POPP was better than COPP in predicting intermediate-dose metrics. The bladder results showed a trend similar to that of the rectum. The correlation coefficient of POPP was significantly greater than that of COPP in < 62 Gy (82% of the prescribed dose) region for IMRT and in < 55 Gy (73% of the prescribed dose) region for VMAT regarding the rectum (p < 0.05). CONCLUSIONS: POPP is superior to COPP for creating predictive models at an intermediate-dose level. Because rectal bleeding and bladder toxicity can be associated with intermediate-doses as well as high-doses, it is important to predict dose-volume metrics for various dose levels. POPP is a useful parameter for predicting dose-volume metrics and assisting the generation of treatment plans.

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions.

Diaryliodonium(III) salts are versatile reagents that exhibit a range of reactions, both in the presence and absence of metal catalysts. In this study, we developed efficient synthetic methods for the preparation of aryl(TMP)iodonium(III) carboxylates, by reaction of (diacetoxyiodo)arenes or iodosoarenes with 1,3,5-trimethoxybenzene in the presence of a diverse range of organocarboxylic acids. These reactions were conducted under mild conditions using the trimethoxyphenyl (TMP) group as an auxiliary, without the need for additives, excess reagents, or counterion exchange in further steps. These protocols are compatible with a wide range of substituents on (hetero)aryl iodine(III) compounds, including electron-rich, electron-poor, sterically congested, and acid-labile groups, as well as a broad range of aliphatic and aromatic carboxylic acids for the synthesis of diverse aryl(TMP)iodonium(III) carboxylates in high yields. This method allows for the hybridization of complex bioactive and fluorescent-labeled carboxylic acids with diaryliodonium(III) salts.

Wavefront restoration from lateral shearing data using spectral interpolation.

Although a lateral-shear interferometer is robust against optical component vibrations, its interferogram provides information about differential wavefronts rather than the wavefronts themselves, resulting in the loss of specific frequency components. Previous studies have addressed this limitation by measuring four interferograms with different shear amounts to accurately restore the two-dimensional wavefront. This study proposes a technique that employs spectral interpolation to reduce the number of required interferograms. The proposed approach introduces an origin-shift technique for accurate spectral interpolation, which in turn is implemented by combining two methods: natural extension and least-squares determination of ambiguities in uniform biases. Numerical simulations confirmed that the proposed method accurately restored a two-dimensional wavefront from just two interferograms, thereby indicating its potential to address the limitations of the lateral-shear interferometer.

Eribulin improves tumor oxygenation demonstrated by 18F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models.

PURPOSE: Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-18F-fluoropropyl)-2-nitroimidazole (18F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. METHODS: Mice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with 18F-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation, 18F-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation. RESULTS: Eribulin significantly reduced 18F-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in 18F-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with 18F-DiFA accumulation. CONCLUSION: These results demonstrated that 18F-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.

Ligand release from silicon phthalocyanine dyes triggered by X-ray irradiation.

Ligand release from silicon phthalocyanine (SiPc) dyes triggered by near-infrared (NIR) light is a key photochemical reaction involving caged compounds based on SiPc. Although NIR light is relatively permeable compared with visible light, this light can be attenuated by tissue absorption and scattering; therefore, using light to induce photochemical reactions deep inside the body is difficult. Herein, because X-rays are highly permeable and can produce radicals through the radiolysis of water, we investigated whether the axial ligands of SiPcs can be cleaved using X-ray irradiation. SiPcs with different axial ligands (alkoxy, siloxy, oxycarbonyl, and phenoxy groups) were irradiated with X-rays under hypoxic conditions. We found that the axial ligands were cleaved via reactions with hydrated electrons (e-aq), not OH radicals, generated from water in response to X-ray irradiation, and SiPc with alkoxy groups exhibited the highest cleavage efficiency. A quantitative investigation revealed that X-ray-induced axial ligand cleavage proceeds via a radical chain reaction. The reaction is expected to be applicable to the molecular design of X-ray-activatable functional molecules in the future.

Treatment outcomes of stereotactic body radiation therapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinomas.

AIM: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/ß ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.

Cone-beam computed tomography versus computed tomography-guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score-matched analysis.

BACKGROUND AND OBJECTIVE: CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis. METHODS: Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics. RESULTS: We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001). CONCLUSION: CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.

Fundamental study on quality assurance (QA) procedures for a real-time tumor tracking radiotherapy (RTRT) system from the viewpoint of imaging devices.

PURPOSE: The real-time tumor tracking radiotherapy (RTRT) system requires periodic quality assurance (QA) and quality control. The goal of this study is to propose QA procedures from the viewpoint of imaging devices in the RTRT system. METHODS: Tracking by the RTRT system (equips two sets of colored image intensifiers (colored I.I.s) fluoroscopy units) for the moving gold-marker (diameter 2.0 mm) in a rotating phantom were performed under various X-ray conditions. To analyze the relationship between fluoroscopic image quality and precision of gold marker coordinate calculation, the standard deviation of the 3D coordinate (σ3D [mm]) of the gold marker, the mean of the pattern recognition score (PRS) and the standard deviation of the distance between rays (DBR) (σDBR [mm]) were evaluated. RESULTS: When tracking with speed of 10-60 mm/s, σDBR increased, though the mean PRS did not change significantly (p>0.05). On the contrary, the mean PRS increased depending on the integral noise equivalent quanta (∫NEQ) that is an indicator of image quality calculated from the modulation transfer function (MTF) as an indicator of spatial resolution and the noise power spectrum (NPS) as an indicator of noise characteristic. CONCLUSION: The indicators of NEQ, MTF, and NPS were useful for managing the tracking accuracy of the RTRT system. We propose observing the change of these indicators as additional QA procedures for each imaging device from the commissioning baseline.

Dynamic gating window technique for the reduction of dosimetric error in respiratory-gated spot-scanning particle therapy: An initial phantom study using patient tumor trajectory data.

Spot-scanning particle therapy possesses advantages, such as high conformity to the target and efficient energy utilization compared with those of the passive scattering irradiation technique. However, this irradiation technique is sensitive to target motion. In the current clinical situation, some motion management techniques, such as respiratory-gated irradiation, which uses an external or internal surrogate, have been clinically applied. In surrogate-based gating, the size of the gating window is fixed during the treatment in the current treatment system. In this study, we propose a dynamic gating window technique, which optimizes the size of gating window for each spot by considering a possible dosimetric error. The effectiveness of the dynamic gating window technique was evaluated by simulating irradiation using a moving target in a water phantom. In dosimetric characteristics comparison, the dynamic gating window technique exhibited better performance in all evaluation volumes with different effective depths compared with that of the fixed gate approach. The variation of dosimetric characteristics according to the target depth was small in dynamic gate compared to fixed gate. These results suggest that the dynamic gating window technique can maintain an acceptable dose distribution regardless of the target depth. The overall gating efficiency of the dynamic gate was approximately equal or greater than that of the fixed gating window. In dynamic gate, as the target depth becomes shallower, the gating efficiency will be reduced, although dosimetric characteristics will be maintained regardless of the target depth. The results of this study suggest that the proposed gating technique may potentially improve the dose distribution. However, additional evaluations should be undertaken in the future to determine clinical applicability by assuming the specifications of the treatment system and clinical situation.

Difference in LET-based biological doses between IMPT optimization techniques: Robust and PTV-based optimizations.

PURPOSE: While a large amount of experimental data suggest that the proton relative biological effectiveness (RBE) varies with both physical and biological parameters, current commercial treatment planning systems (TPS) use the constant RBE instead of variable RBE models, neglecting the dependence of RBE on the linear energy transfer (LET). To conduct as accurate a clinical evaluation as possible in this circumstance, it is desirable that the dosimetric parameters derived by TPS ( D RBE = 1.1 ) are close to the "true" values derived with the variable RBE models ( D v RBE ). As such, in this study, the closeness of D RBE = 1.1 to D v RBE was compared between planning target volume (PTV)-based and robust plans. METHODS: Intensity-modulated proton therapy (IMPT) treatment plans for two Radiation Therapy Oncology Group (RTOG) phantom cases and four nasopharyngeal cases were created using the PTV-based and robust optimizations, under the assumption of a constant RBE of 1.1. First, the physical dose and dose-averaged LET (LETd ) distributions were obtained using the analytical calculation method, based on the pencil beam algorithm. Next, D v RBE was calculated using three different RBE models. The deviation of D v RBE from D RBE = 1.1 was evaluated with D99 and Dmax , which have been used as the evaluation indices for clinical target volume (CTV) and organs at risk (OARs), respectively. The influence of the distance between the OAR and CTV on the results was also investigated. As a measure of distance, the closest distance and the overlapped volume histogram were used for the RTOG phantom and nasopharyngeal cases, respectively. RESULTS: As for the OAR, the deviations of D max v RBE from D max RBE = 1.1 were always smaller in robust plans than in PTV-based plans in all RBE models. The deviation would tend to increase as the OAR was located closer to the CTV in both optimization techniques. As for the CTV, the deviations of D 99 v RBE from D 99 RBE = 1.1 were comparable between the two optimization techniques, regardless of the distance between the CTV and the OAR. CONCLUSION: Robust optimization was found to be more favorable than PTV-based optimization in that the results presented by TPS were closer to the "true" values and that the clinical evaluation based on TPS was more reliable.

Percutaneous insertion of hepatic fiducial true-spherical markers for real-time adaptive radiotherapy.

Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating.Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed.Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver (n = 4) or intrahepatic vessels (n = 5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered.Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.

Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity-modulated radiotherapy.

PURPOSE: Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. METHODS: Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (Vp ), and D99 of the CTV were evaluated. RESULTS: The organ motion was the largest in the superior-inferior direction (10.1 ± 4.5 mm [average ± SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a ± 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in Vp and D99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D99 was less than 1% of the prescribed dose. CONCLUSIONS: There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.

[Effectiveness of Ramucirumab Therapy for Advanced Gastric Cancer after Stent Placement for Esophagogastric Junction Carcinoma Obstruction-A Case Report].

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.

Structural basis of the broad substrate tolerance of the antibody 7B9-catalyzed hydrolysis of p-nitrobenzyl esters.

Catalytic antibody 7B9, which was elicited against p-nitrobenzyl phosphonate transition-state analogue (TSA) 1, hydrolyzes a wide range of p-nitrobenzyl monoesters and thus shows broad substrate tolerance. To reveal the molecular basis of this substrate tolerance, the 7B9 Fab fragment complexed with p-nitrobenzyl ethylphosphonate 2 was crystallized and the three-dimensional structure was determined. The crystal structure showed that the strongly antigenic p-nitrobenzyl moiety occupied a relatively shallow antigen-combining site and therefore the alkyl moiety was located outside the pocket. These results support the observed broad substrate tolerance of 7B9 and help rationalize how 7B9 can catalyze various p-nitrobenzyl ester derivatives. The crystal structure also showed that three amino acid residues (AsnH33, SerH95, and ArgL96) were placed in key positions to form hydrogen bonds with the phosphonate oxygens of the transitions-state analogue. In addition, the role of these amino acid residues was examined by site-directed mutagenesis to alanine: all mutants (AsnH33Ala, SerH95Ala, and ArgL96Ala) showed no detectable catalytic activity. Coupling the findings from our structural studies with these mutagenesis results clarified the structural basis of the observed broad substrate tolerance of antibody 7B9-catalyzed hydrolyses. Our findings provide new strategies for the generation of catalytic antibodies that accept a broad range of substrates, aiding their practical application in synthetic organic chemistry.

Development of protein degradation inducers of oncogenic BCR-ABL protein by conjugation of ABL kinase inhibitors and IAP ligands.

Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein. We have devised a protein knockdown system by hybrid molecules named Specific and Non-genetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER), which is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins, and a couple of SNIPER(ABL) against BCR-ABL protein have been developed recently. In this study, we tested various combinations of ABL inhibitors and IAP ligands, and the linker was optimized for protein knockdown activity of SNIPER(ABL). The resulting SNIPER(ABL)-39, in which dasatinib is conjugated to an IAP ligand LCL161 derivative by polyethylene glycol (PEG) × 3 linker, shows a potent activity to degrade the BCR-ABL protein. Mechanistic analysis suggested that both cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) play a role in the degradation of BCR-ABL protein. Consistent with the degradation of BCR-ABL protein, the SNIPER(ABL)-39 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and Crk like proto-oncogene (CrkL), and suppressed the growth of BCR-ABL-positive CML cells. These results suggest that SNIPER(ABL)-39 could be a candidate for a degradation-based novel anti-cancer drug against BCR-ABL-positive CML.

Weighted reconstruction of three-dimensional refractive index in interferometric tomography.

Interferometric tomography can reconstruct 3D refractive-index distributions through phase-shift measurements for different beam angles. To reconstruct a complex refractive-index distribution, many projections along different directions are required. For the purpose of increasing the number of the projections, we earlier proposed a beam-angle-controllable interferometer with mechanical stages; however, the quality of reconstructed distribution by conventional algorithms was poor because the background fringes cannot be precisely controlled. To improve the quality, we propose a weighted reconstruction algorithm that can consider projection errors. We demonstrate the validity of the weighted reconstruction through simulations and a reconstruction from experimental data for three candle flames.

Integration of DPC and clinical microbiological data in Japan reveals importance of confirming a negative follow-up blood culture in patients with MRSA bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is one of the commonest and most life-threatening of all infectious diseases. The morbidity and mortality rates associated with MRSA bacteremia are higher than those associated with bacteremia caused by other pathogens. A common guideline in MRSA bacteremia treatment is to confirm bacteremia clearance through additional blood cultures 2-4 days after initial positive cultures and as needed thereafter. However, no study has presented statistical evidence of how and to what extent confirming a negative follow-up blood culture impacts clinical outcome. We present this evidence for the first time, by combining clinical microbiological data of blood cultures and the DPC administrative claims database; both had been systematically accumulated through routine medical care in hospitals. We used electronic medical records to investigate the clinical background and infection source in detail. By analyzing data from a university hospital, we revealed how survival curves change when a negative follow-up blood culture is confirmed. We also demonstrated confirmation of a negative culture is significantly associated with clinical outcomes: there was a more than three-fold increase in mortality risk (after adjusting for clinical background) if a negative blood culture was not confirmed within 14 days of the initial positive blood culture. Although we used data from only one university hospital, our novel approach and results will be a basis for future studies in several hospitals in Japan to provide statistical evidence of the clinical importance of confirming a negative follow-up blood culture in bacteremia patients, including those with MRSA infections.

[Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully Treated by Intrapleural Administration of Diluted Fibrin Glue;Report of a Case].

Malignant pleural mesothelioma sometimes accompanies intractable neumothorax due to the visceral pleural invasion of the tumor. A 68-years-old man was found to have massive pleural effusion and pleural mass combined with pneumothorax by computed tomography(CT). CT guided biopsy revealed the mass to be malignant pleural mesothelioma. Since continuous air leakage was observed by chest drainage, pleurodesis by OK-432 twice and bronchial occlusion by Endobronchial Watanabe Spigot (EWS)were performed. But air leakage continued, and the surgery was performed, however the treatment failed to stop the air leakage. Finally, the intrapleural administration of diluted fibrin glue was challenged and the air leakage stopped immediately after the treatment.

Prospective phase II study of image-guided local boost using a real-time tumor-tracking radiotherapy (RTRT) system for locally advanced bladder cancer.

OBJECTIVE: The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. METHODS: Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than ±2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. RESULTS: Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%. CONCLUSIONS: Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients' quality of life.