Faculty Profiles - MITSUHASHI Toshiharu

Papers - MITSUHASHI Toshiharu

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Radiofrequency ablation of pulmonary tumors near the diaphragm Reviewed

T. Iguchi, T. Hiraki, H. Gobara, H. Fujiwara, J. Sakurai, Y. Matsui, T. Mitsuhashi, S. Toyooka, S. Kanazawa

Diagnostic and Interventional Imaging 98 ( 7-8 ) 535 - 541 2017.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Masson SAS

Purpose To retrospectively evaluate the feasibility, safety, and efficacy of radiofrequency ablation (RFA) of lung tumors located near the diaphragm. Materials and methods A total of 26 patients (15 men, 11 women
mean age, 61.5 years ± 13.0 [SD]) with a total of 29 lung tumors near the diaphragm (i.e., distance &lt
10 mm) were included. Mean tumor diameter was 11.0 mm ± 5.3 (SD) (range, 2–23 mm). Efficacy of RFA, number of adverse events and number of adverse events with a grade ≥ 3, based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, were compared between patients with lung tumors near the diaphragm and a control group of patients with more distally located lung tumors (i.e., distance ≥ 10 mm). Results RFA was technically feasible for all tumors near the diaphragm. Four grade 3 adverse events (1 pneumothorax requiring pleurodesis and 3 phrenic nerve injuries) were observed. No grade ≥ 4 adverse events were reported. The median follow-up period for tumors near the diaphragm was 18.3 months. Local progression was observed 3.3 months after RFA in 1 tumor. The technique efficacy rates were 96.2% at 1 year and 96.2% at 2 years and were not different, from those observed in control subjects (186 tumors
P = 0.839). Shoulder pain (P &lt
0.001) and grade 1 pleural effusion (P &lt
0.001) were more frequently observed in patients with lung tumor near the diaphragm. The rates of grade ≥ 3 adverse events did not significantly differ between tumors near the diaphragm (4/26 sessions) and the controls (7/133 sessions) (P = 0.083). Conclusion RFA is a feasible and effective therapeutic option for lung tumors located near the diaphragm. However, it conveys a higher rate of shoulder pain and asymptomatic pleural effusion by comparison with more distant lung tumors.

DOI： 10.1016/j.diii.2017.01.008

Lesion Size on Ultrasonography Predicts Potential Invasion in Ductal Carcinoma in situ Preoperatively Diagnosed by Breast Needle Biopsy. Reviewed

Kyoko Shimoyama, Tomo Osako, Toshiharu Mitsuhashi, Futoshi Akiyama, Takuji Iwase

Acta medica Okayama 71 ( 3 ) 233 - 240 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Ductal carcinoma in situ (DCIS) of the breast has no potential to metastasize, but over 20% of cases preoperatively diagnosed as DCIS are upstaged on final pathology. The rates of upstaging and the predictors for invasion on final pathology were evaluated. For 240 primary breast cancers, radiological findings on mammography, ultrasonography, and magnetic resonance imaging were investigated along with pathological and clinical information. Univariate and multivariate analyses were performed to identify predictors of potential invasion. Of the 240 breast cancers, 68 (28.3%) showed invasion on final pathology, and 5 (2.5%) had sentinel node metastasis. The multivariate analysis identified five independent predictors: non-mass lesions >2.4 cm on ultrasonography (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.02-7.95, p=0.047), comedo-type histology (OR 6.89, 95% CI 1.89-25.08, p<0.01), solid-type histology (OR 7.97, 95% CI 2.08-30.49, p<0.01), palpable mass (OR 2.63, 95% CI 1.05-6.64, p=0.04), and bloody nipple discharge (OR 4.61, 95% CI 1.20-17.66, p=0.02). These five predictors were associated with invasion on final pathology and may help select candidates for sentinel node biopsy.

DOI： 10.18926/AMO/55206

Disappearance of Renal Cysts Included in Ice Ball During Cryoablation of Renal-Cell Carcinoma: A Potential Therapy for Symptomatic Renal Cysts? Reviewed International journal

Mitsuko Yodoya, Takao Hiraki, Toshihiro Iguchi, Hiroyasu Fujiwara, Yusuke Matsui, Yoshihisa Masaoka, Jun Sakurai, Toshiharu Mitsuhashi, Hideo Gobara, Susumu Kanazawa

Journal of vascular and interventional radiology : JVIR 28 ( 6 ) 869 - 876 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

PURPOSE: To retrospectively evaluate the effect of cryoablation of renal-cell carcinoma on nearby renal cysts with the goal to investigate the potential for an alternative therapy to treat symptomatic renal cysts. MATERIALS AND METHODS: The study population comprised 46 cysts (mean size, 12 mm; range, 5-43 mm) that were within or near the ice ball during cryoablation in 22 patients. Size change of each cyst was evaluated via enhanced CT or MR imaging before and 1, 3, 6, and 12 months after cryoablation. Forty-one cysts were also followed after 12 months. Variables including positional relationship between the cyst and the ice ball were evaluated via linear regression analysis using generalized estimating equation models to determine which factors affected cyst shrinkage rate at 12 months. RESULTS: Fifteen, 12, and 19 cysts were completely included in, partially included in, or excluded from the ice ball, respectively. The overall shrinkage rate was 62%, and 57% of cysts (26 of 46) had disappeared at 12 months. Only the relationship between the cyst and the ice ball was significantly (P < .001) associated with cyst shrinkage rate. Cyst disappearance rates at 12 months were 100% (15 of 15), 67% (8 of 12), and 16% (3 of 19) for cysts completely included, partially included, and excluded from the ice ball, respectively. Among the 22 cysts that disappeared at 12 months and continued to be followed, none recurred after 12 months. CONCLUSIONS: All renal cysts that were completely included in the ice ball disappeared after cryoablation, demonstrating the potential utility of cryoablation as an alternative therapy for symptomatic renal cysts.

DOI： 10.1016/j.jvir.2017.02.027

One-year outcomes of a treat-and-extend regimen of intravitreal aflibercept for polypoidal choroidal vasculopathy. Reviewed

Mio Hosokawa, Yuki Morizane, Masayuki Hirano, Shuhei Kimura, Fumiaki Kumase, Yusuke Shiode, Shinichiro Doi, Shinji Toshima, Mika Hosogi, Atsushi Fujiwara, Toshiharu Mitsuhashi, Fumio Shiraga

Japanese journal of ophthalmology 61 ( 2 ) 150 - 158 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

PURPOSE: To evaluate the 1-year treatment outcomes of intravitreal aflibercept injections (IVA) using a treat-and-extend regimen for polypoidal choroidal vasculopathy (PCV). METHODS: Thirty-seven eyes with treatment-naive PCV treated with IVA using a treat-and-extend regimen for 1 year were reviewed retrospectively. The main outcome measures were changes in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and the treatment interval at 1 year. The predictive factors for patients who could not continue to extend the treatment interval because of poor response to IVA or recurrence were analyzed. RESULTS: The mean logarithm of the minimum angle of resolution BCVA improved from 0.37 at baseline to 0.21 at 1 year (P < 0.001). The mean CRT decreased from 342.3 μm at baseline to 196.6 μm at 1 year (P < 0.001). The mean treatment interval was 9.7 weeks at 1 year (4 weeks in 11 eyes [29.7%], 6 weeks in 1 eye [2.7%], 8 weeks in 2 eyes [5.4%], 10 weeks in 1 eye [2.7%], and 12 weeks in 22 eyes [59.5%]). A larger number of polypoidal lesions at baseline was predictive for patients who could not continue to extend the treatment interval. CONCLUSIONS: IVA using a treat-and-extend regimen is effective for improving BCVA and CRT in eyes with PCV.

DOI： 10.1007/s10384-016-0492-7

Interfractional Seminal Vesicle Motion Relative to the Prostate Gland for Image-guided Radiotherapy for Prostate Cancer with/without Androgen Deprivation Therapy: A Retrospective Cohort Study. Reviewed

Takahiro Waki, Kuniaki Katsui, Toshiharu Mitsuhashi, Takeshi Ogata, Norihisa Katayama, Mitsuhiro Takemoto, Yasutomo Nasu, Hiromi Kumon, Susumu Kanazawa

Acta medica Okayama 71 ( 1 ) 31 - 39 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

We investigated differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs' length and motion by computed tomography (CT) to determine the ADT's effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients' SV length was significantly shorter than the non-ADT patients'. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.1- 11.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and non- ADT patients in terms of interfractional motion of the SV tips and the SVs' center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used.

DOI： 10.18926/AMO/54823

Clinical Epidemiology and Treatment of Febrile and Afebrile Convulsions With Mild Gastroenteritis: A Multicenter Study. Reviewed International journal

Yousuke Higuchi, Toshihide Kubo, Toshiharu Mitsuhashi, Naoko Nakamura, Ichiro Yokota, Osamu Komiyama, Isamu Kamimaki, Shigenori Yamamoto, Yasushi Uchida, Kyoko Watanabe, Hironori Yamashita, Shigeki Tanaka, Kosei Iguchi, Ryouji Ichimi, Shinichiro Miyagawa, Toshimitsu Takayanagi, Hiroshi Koga, Akinori Shukuya, Akiko Saito, Keizo Horibe

Pediatric neurology 67 78 - 84 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

BACKGROUND: We investigated features and responses to treatment in patients with febrile and afebrile convulsions with mild gastroenteritis and characterized convulsions with rotavirus and norovirus gastroenteritis. METHODS: We conducted a prospective, observational study to evaluate patients with febrile and afebrile convulsions with mild gastroenteritis who were hospitalized between November 2011 and March 2014 at 13 facilities in the National Hospital Organization. We classified the patients into two groups: presence or absence of fever. We investigated the background, clinical and laboratory characteristics, viral antigen in stool, and efficacy of anticonvulsant drugs. RESULTS: Of 126 patients enrolled in this study, 50 were febrile (Fc group) and 76 were afebrile (aFc group). A family history of febrile seizures was significantly more frequent in the Fc group than in the aFc group (28.0% vs 9.2%, P = 0.005). Clinical characteristics were similar between the rotavirus and norovirus groups, but fever was significantly more frequent in the rotavirus group (46.2% vs 8.3%, P < 0.001). Serum sodium levels were significantly negatively related to the number of seizures in the aFc group (β = -0.13; 95% confidence interval, -0.24, -0.03; P = 0.01). Carbamazepine was significantly more efficacious than diazepam suppositories in the aFc group (odds ratio = 49.3, 95% confidence interval, 2.35, 1037; P = 0.01). CONCLUSION: Febrile convulsions with mild gastroenteritis show characteristics of both febrile seizures and convulsions with mild gastroenteritis. Carbamazepine is optimal for convulsions with mild gastroenteritis. Clinical features of convulsions with rotavirus and norovirus gastroenteritis are similar, except for fever. Serum sodium levels may play a major role in the onset of convulsions with mild gastroenteritis.

DOI： 10.1016/j.pediatrneurol.2016.05.011

Radiofrequency ablation of pulmonary metastases from sarcoma: single-center retrospective evaluation of 46 patients. Reviewed

Takuya Sato, Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Jun Sakurai, Yusuke Matsui, Toshiharu Mitsuhashi, Junichi Soh, Shinichi Toyooka, Susumu Kanazawa

Japanese journal of radiology 35 ( 2 ) 61 - 67 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

PURPOSE: This retrospective, single-center study evaluated radiofrequency (RF) ablation for pulmonary metastases of sarcoma. MATERIALS AND METHODS: Forty-six patients with sarcoma (144 pulmonary metastases) underwent 88 RF ablation sessions. Data regarding local tumor progression, efficacy, procedural adverse events (AEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0), overall survival (OS), and OS-associated prognostic factors were retrospectively evaluated using univariate analyses. RESULTS: Local progression occurred in 22 of 144 tumors (15.3%). Primary and secondary efficacy rates were 83.5 and 90.0% at 1 year and 76.3 and 81.4% at 2 years, respectively. Seventy-three grade 1 AEs, 33 grade 2 AEs, and no grade ≥ 3 AEs were observed. Twenty-eight patients (60.9%) remained alive and 18 died, yielding 1-, 2-, and 3-year OS rates of 80.6, 70.1, and 47.1% (median survival time, 31.7 months). Univariate analysis revealed extrapulmonary metastasis (P = 0.005), noncurative RF ablation (P = 0.009), and a post-RF ablation disease-free interval of ≤12 months (P = 0.015) as significant negative prognostic factors. CONCLUSION: RF ablation is safe, offers good local control, and may be a viable treatment option for pulmonary metastasis of sarcoma.

DOI： 10.1007/s11604-016-0601-z

A typology of four notions of confounding in epidemiology. Reviewed

Etsuji Suzuki, Toshiharu Mitsuhashi, Toshihide Tsuda, Eiji Yamamoto

Journal of epidemiology 27 ( 2 ) 49 - 55 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Confounding is a major concern in epidemiology. Despite its significance, the different notions of confounding have not been fully appreciated in the literature, leading to confusion of causal concepts in epidemiology. In this article, we aim to highlight the importance of differentiating between the subtly different notions of confounding from the perspective of counterfactual reasoning. By using a simple example, we illustrate the significance of considering the distribution of response types to distinguish causation from association, highlighting that confounding depends not only on the population chosen as the target of inference, but also on the notions of confounding in distribution and confounding in measure. This point has been relatively underappreciated, partly because some literature on the concept of confounding has only used the exposed and unexposed groups as the target populations, while it would be helpful to use the total population as the target population. Moreover, to clarify a further distinction between confounding "in expectation" and "realized" confounding, we illustrate the usefulness of examining the distribution of exposure status in the target population. To grasp the explicit distinction between confounding in expectation and realized confounding, we need to understand the mechanism that generates exposure events, not the product of that mechanism. Finally, we graphically illustrate this point, highlighting the usefulness of directed acyclic graphs in examining the presence of confounding in distribution, in the notion of confounding in expectation.

DOI： 10.1016/j.je.2016.09.003

Impact of Cushing's sign in the prehospital setting on predicting the need for immediate neurosurgical intervention in trauma patients: a nationwide retrospective observational study. Reviewed International journal

Tetsuya Yumoto, Toshiharu Mitsuhashi, Yasuaki Yamakawa, Atsuyoshi Iida, Nobuyuki Nosaka, Kohei Tsukahara, Hiromichi Naito, Atsunori Nakao

Scandinavian journal of trauma, resuscitation and emergency medicine 24 ( 1 ) 147 - 147 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

BACKGROUND: Cushing's reflex usually results from intracranial hypertension. Although Cushing's sign can implicate severe traumatic brain injury (TBI) in injured patients, no major investigations have been made. The purpose of this study was to assess the predictability of life-threatening brain injury requiring immediate neurosurgical intervention (LT-BI) among trauma patients with Cushing's sign in the prehospital setting. METHODS: This was a retrospective study using data from the Japan Trauma Data Bank from the period of 2010 to 2014. Patients 16 years old or older with blunt mechanisms of injury who were transported directly from the scene and Glasgow Coma Scale for eye opening of one in the prehospital setting were included. LT-BI was defined as patients requiring burr hole evacuation or craniotomy within 24 h of hospital arrival and patients who were non-survivors due to isolated severe TBI. Prehospital systolic blood pressure (pSBP) and heart rate (pHR) were assessed using area under the receiver operating characteristic curve (AUROC) and multiple logistic regression analysis to predict LT-BI. RESULTS: Of 6332 eligible patients, 1859 (29%) exhibited LT-BI. AUROC of LT-BI using pSBP and pHR was 0.666 (95% confidence interval (CI); 0.652-0.681, P < 0.001), and 0.578 (95% CI; 0.563-0.594, P < 0.001), respectively. AUROC of pSBP was the highest among the 60 ≤ pHR ≤ 99 subgroup, of which AUROC was 0.680 (95% CI; 0.662-0.699, P < 0.001). Multiple logistic regression analysis showed that the higher the pSBP and the lower the pHR, the more likely that the patients had LT-BI. In a group with pSBP ≥ 180 mmHg and pHR ≤ 59 beats/min, the odds ratio and 95% CI of LT-BI after adjusting for age, sex, and severity of injuries to other body regions was 4.77 (2.85-7.97), P < 0.001 was compared with the reference group, which was defined as patients with normal vital signs. DISCUSSION: Our study has found that the combination of hypertension and bradycardia, which are the components of Cushing's sign without eye opening in the prehospital setting was a weak but a significant predictor of LT-BI, or death due to possible isolated severe TBI. CONCLUSIONS: Prehospital Cushing's sign with disturbed level of consciousness in trauma patients was a weak but significant predictor of the need for immediate neurosurgical intervention.

DOI： 10.1186/s13049-016-0341-1

Fracture of totally implanted central venous access devices: a propensity-score-matched comparison of risks for Groshong silicone versus polyurethane catheters. Reviewed International journal

Soichi Kojima, Takao Hiraki, Hideo Gobara, Toshihiro Iguchi, Hiroyasu Fujiwara, Yusuke Matsui, Toshiharu Mitsuhashi, Susumu Kanazawa

The journal of vascular access 17 ( 6 ) 535 - 541 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WICHTIG PUBLISHING

PURPOSE: To evaluate retrospectively the fracture risk of totally implanted venous access devices connected to Groshong silicone (SC) versus polyurethane (PU) catheters, inserted via the internal jugular vein. MATERIALS AND METHODS: The study population comprised 384 SC and 221 PU central venous catheters implanted via the internal jugular vein. The presence of catheter fracture was evaluated. Variables possibly related to catheter fracture were evaluated. First, in order to determine the factors associated with fracture, fracture rates were compared with the log-rank test between the two groups divided by each of the variables. Then, in order to adjust for potential confounders, propensity-score matching of the variables was employed in the two catheter groups. Finally, the rates of fracture were compared between the two propensity-score-matched catheter groups. RESULTS: There were 16 cases of catheter fracture, for an overall fracture percentage of 2.6% (16/605). All 16 cases of fracture occurred in the SC catheter group. Smaller patient body mass index (p = 0.039), deeper catheter tip position (p = 0.022), and SC catheters (p = 0.019) were significantly associated with fracture. With the propensity-score-matching method, 180 cases were selected in each catheter group. Comparison of the two propensity-score-matched groups showed that fracture rates for SC catheters remained significantly (p = 0.018) higher than those for PU catheters. CONCLUSIONS: Ports connected to Groshong SC catheters - when implanted via the internal jugular vein - posed a higher risk of fracture than did ports connected to PU catheters.

DOI： 10.5301/jva.5000606

Errors in causal inference: an organizational schema for systematic error and random error. Reviewed International journal

Etsuji Suzuki, Toshihide Tsuda, Toshiharu Mitsuhashi, Mohammad Ali Mansournia, Eiji Yamamoto

Annals of epidemiology 26 ( 11 ) 788 - 793 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

PURPOSE: To provide an organizational schema for systematic error and random error in estimating causal measures, aimed at clarifying the concept of errors from the perspective of causal inference. METHODS: We propose to divide systematic error into structural error and analytic error. With regard to random error, our schema shows its four major sources: nondeterministic counterfactuals, sampling variability, a mechanism that generates exposure events and measurement variability. RESULTS: Structural error is defined from the perspective of counterfactual reasoning and divided into nonexchangeability bias (which comprises confounding bias and selection bias) and measurement bias. Directed acyclic graphs are useful to illustrate this kind of error. Nonexchangeability bias implies a lack of "exchangeability" between the selected exposed and unexposed groups. A lack of exchangeability is not a primary concern of measurement bias, justifying its separation from confounding bias and selection bias. Many forms of analytic errors result from the small-sample properties of the estimator used and vanish asymptotically. Analytic error also results from wrong (misspecified) statistical models and inappropriate statistical methods. CONCLUSIONS: Our organizational schema is helpful for understanding the relationship between systematic error and random error from a previously less investigated aspect, enabling us to better understand the relationship between accuracy, validity, and precision.

DOI： 10.1016/j.annepidem.2016.09.008

Single Center Prospective Phase II Trial of CT-guided Radiofrequency Ablation for Pulmonary Metastases from Colorectal Cancer (SCIRO-1401). Reviewed

Jun Sakurai, Yusuke Matsui, Takao Hiraki, Toshihiro Iguchi, Hiroyasu Fujiwara, Hideo Gobara, Toshiharu Mitsuhashi, Takeshi Nagasaka, Susumu Kanazawa

Acta medica Okayama 70 ( 4 ) 317 - 21 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The present single center prospective phase II clinical trial is designed to evaluate the efficacy and safety of percutaneous radiofrequency (RF) ablation for colorectal lung metastases. Patients who have colorectal lung metastases without extrapulmonary metastases are included in this study. The primary endpoint is 3-year overall survival (OS) after RF ablation. The secondary endpoints are the prevalence of adverse events within 4 weeks, local tumor progression rate, 1- and 5-year OS, cause-specific survival, and relapse-free survival. The recruitment of patients commenced in July 2014, and the enrolment of 45 patients is intended over the 3 years of study period.

DOI： 10.18926/AMO/54512

A phase 1, dose-finding and pharmacokinetic study of gemcitabine with nab-paclitaxel in patients with metastatic breast cancer. Reviewed International journal

Seiji Yoshitomi, Naruto Taira, Hiroyoshi Doihara, Taeko Mizoo, Tomohiro Nogami, Takayuki Iwamoto, Takayuki Motoki, Tadahiko Shien, Yutaka Ogasawara, Junji Matsuoka, Hisashi Tsuji, Toshiharu Mitsuhashi

Cancer chemotherapy and pharmacology 78 ( 2 ) 289 - 94 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

PURPOSE: Gemcitabine (Gem) with paclitaxel (Pac) is used for patients with metastatic breast cancer who require cytoreduction with manageable toxicities. Nanoparticle albumin-bound (nab)-Pac exhibits better efficacy and reduces the risk of hypersensitivity reactions associated with solvent-based Pac. Therefore, Gem plus nab-Pac (GA) therapy may be effective for metastatic breast cancer. The purpose of this study was to determine the maximum tolerated dose for GA therapy. METHODS: The subjects were patients with metastatic breast cancer with performance status 0 or 1 and normal hepatic, renal and marrow function. Leukopenia, neutropenia or thrombocytopenia of grade 4, neutropenic fever, or non-hematological toxicity of grade 3 or higher during the 1st cycle, and chemotherapy-induced peripheral neurotoxicity of grade 2 or higher at the end of the 1st cycle were defined as dose-limiting toxicities (DLTs). Gem (1250 mg/m(2)) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m(2) (cohort 1) and escalated to 220 mg/m(2) (cohort 2) and 260 mg/m(2) (cohort 3) on day 1 of the 21-day cycle, using a 3 + 3 design. RESULTS: Nine patients (n = 3, 3, and 3 in cohorts 1, 2, and 3, respectively) were included in the study (median age 56 years; range 43-75 years). DLTs did not occur in any cohorts. CONCLUSIONS: The initial recommend dose in GA therapy is 1250 mg/m(2) Gem and 260 mg/m(2) nab-Pac. It is well known that nab-Pac has cumulative toxicities, and thus the efficacy and safety of GA therapy require validation in a phase 2 study.

DOI： 10.1007/s00280-016-3091-x

Chronic interstitial pneumonia in young patients undergoing lung transplantation or autopsy: clinico-radiologic-pathologic observations from a single institution. Reviewed

Mayu Uka, Toshihiro Iguchi, Katsuya Kato, Hidehiro Hayashi, Ichiro Yamadori, Toshiharu Mitsuhashi, Takahiro Oto, Shuhei Sato, Susumu Kanazawa

Japanese journal of radiology 34 ( 7 ) 515 - 22 2016.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

PURPOSE: To retrospectively evaluate high-resolution computed tomography (HRCT) findings and clinical diagnoses of chronic interstitial pneumonia (IP) with a poor prognosis in young patients (≤50 years). MATERIALS AND METHODS: HRCT images of 8 men and 7 women (mean age 34.8 years) obtained before lung transplantation or autopsy were reviewed. After reviewing whole lung specimens and pathologic diagnoses, all patients were clinically diagnosed according to the 2010 idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) consensus statement. RESULTS: HRCT images revealed intralobular reticular opacity, air cysts, ground glass opacity, traction bronchiectasis, and interlobular septal thickening. Intralobular reticular opacity was the most extensive finding. Abnormal findings existed predominantly in both the peripheral and lower lung zones in only 1 patient. Classifications of HRCT patterns were "UIP" (n = 2), "inconsistent with UIP" (n = 11), and "indeterminate UIP" (n = 2). Multidisciplinary diagnoses were "IPF/UIP" (n = 1), "possible IPF/UIP" (n = 1), "IP with connective tissue disease" (n = 7), "fibrotic nonspecific IP" (n = 1), and "unclassified IP" (n = 5). CONCLUSION: The most extensive HRCT finding was intralobular reticular opacity. Most HRCT images differed from typical IPF/UIP, and IPF/UIP was uncommon in young patients with chronic IP with a poor prognosis.

DOI： 10.1007/s11604-016-0551-5

Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes. Reviewed International journal

Shinji Sakamoto, Manabu Takaki, Yuko Okahisa, Yutaka Mizuki, Masatoshi Inagaki, Hiroshi Ujike, Toshiharu Mitsuhashi, Soshi Takao, Masashi Ikeda, Yosuke Uchitomi, Nakao Iwata, Norihito Yamada

Journal of human genetics 61 ( 4 ) 329 - 34 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Many patients with schizophrenia have poor clinical and social outcomes. Some risk alleles closely related to the onset of schizophrenia have been reported to be associated with their clinical phenotypes, but the direct relationship between genetic vulnerability to schizophrenia and clinical/social outcomes of schizophrenia, as evaluated by both practical clinical scales and 'real-world' function, has not been investigated. We evaluated the clinical and social outcomes of 455 Japanese patients with schizophrenia by severity of illness according to the Clinical Global Impression-Severity Scale (CGI-S) and social outcomes by social adjustment/maladjustment at 5 years after the first visit. We examined whether 46 single nucleotide polymorphisms (SNPs) selected from a Japanese genome-wide association study of susceptibility to schizophrenia were associated with clinical and social outcomes. We also investigated the polygenic risk scores of 46 SNPs. Allele-wise association analysis detected three SNPs, including rs2623659 in the CUB and Sushi multiple domains-1 (CSMD1) gene, associated with severity of illness at end point. The severity of illness at end point was associated with treatment response, but not with the severity of illness at baseline. Three SNPs, including rs2294424 in the C6orf105 gene, were associated with social outcomes. Point estimates of odds ratios showed positive relationships between polygenic risk scores and clinical/social outcomes; however, the results were not statistically significant. Because these results are exploratory, we need to replicate them with a larger sample in a future study.

DOI： 10.1038/jhg.2015.153

Radiofrequency Ablation of Lung Tumors Using a Multitined Expandable Electrode: Impact of the Electrode Array Diameter on Local Tumor Progression. Reviewed International journal

Hiroki Ihara, Hideo Gobara, Takao Hiraki, Toshiharu Mitsuhashi, Toshihiro Iguchi, Hiroyasu Fujiwara, Yusuke Matsui, Junichi Soh, Shinichi Toyooka, Susumu Kanazawa

Journal of vascular and interventional radiology : JVIR 27 ( 1 ) 87 - 95 2016.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

PURPOSE: To retrospectively investigate the impact of the electrode array diameter on local tumor progression after lung radiofrequency ablation. MATERIALS AND METHODS: This study included 651 lung tumors treated using multitined expandable electrodes and followed for ≥ 6 months. The mean long-axis tumor diameter was 12 mm ± 7 (range, 2-42 mm). The difference between electrode array diameter and tumor diameter (DAT) was used to investigate the impact of the electrode array diameter. All tumors were classified into 2 groups according to various variables including DAT (≥ 10 mm or < 10 mm). The primary technique efficacy rates were calculated using Kaplan-Meier analysis and compared between the 2 groups of each variable using the log-rank test. In addition, crude and multivariate multilevel survival analyses were performed by sequentially including DAT and the other variables in 5 models. RESULTS: The median DAT for 651 tumors was 12 mm (range, -15 to 24 mm). The technique efficacy rate was significantly lower in the < 10 mm DAT group than in the ≥ 10 mm group (P < .001). In the crude and multivariate multilevel survival analyses, < 10 mm DAT was a significant risk factor for local progression in all models except model 5 (P = .067). In the ≥ 10 mm group, the technique efficacy rates were not significantly different between the 2 ≥ 10 mm DAT subgroups (10 to <15 mm DAT vs ≥ 15 mm DAT). CONCLUSIONS: DAT is an important risk factor for local progression. We recommend an electrode that is ≥ 10 mm larger than the tumor diameter.

DOI： 10.1016/j.jvir.2015.07.025

Predicting pleural invasion using HRCT and 18F-FDG PET/CT in lung adenocarcinoma with pleural contact. Reviewed

Takashi Tanaka, Takayoshi Shinya, Shuhei Sato, Toshiharu Mitsuhashi, Koichi Ichimura, Junichi Soh, Shinichi Toyooka, Mitsumasa Kaji, Shinichiro Miyoshi, Susumu Kanazawa

Annals of nuclear medicine 29 ( 9 ) 757 - 65 2015.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

OBJECTIVE: To evaluate the relevance of high-resolution computed tomography (HRCT) findings and fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake for risk stratification of visceral pleural invasion by lung adenocarcinoma. METHODS: The HRCT findings and (18)F-FDG uptake for lung adenocarcinomas with pleural contact on CT were retrospectively analyzed in 208 consecutive patients (94 females and 114 males; median age, 69.0 years) between January 2009 and December 2013, with institutional review board approval. The HRCT findings and maximum standardized uptake value (SUV max) were recorded for each patient. Multivariate logistic regression was used for statistical analysis, and subgroup analysis stratified for whole tumor size ≤ 3 cm was also performed. RESULTS: Multivariate analysis showed that SUV max [odds ratio (OR) 1.09, 95 % confidence interval (CI) 1.02-1.16, P = 0.014] and obtuse angle (OR 4.14, 95 % CI 1.97-8.74, P < 0.001) were significant independent predictors for visceral pleural invasion. Receiver operating characteristic (ROC) analysis showed that, compared with the multivariate models [area under the curve (Az) 0.819-0.829], SUV max alone (Az 0.815) was useful in predicting visceral pleural invasion. In the subgroup analysis, multivariate analysis showed that SUV max (OR 1.29, 95 % CI 1.12-1.50, P = 0.001) and contact length with the pleura (OR 1.13, 95 % CI 1.05-1.22, P = 0.001) were significant independent predictors for visceral pleural invasion. ROC analysis showed that SUV max alone (Az 0.844) showed similar diagnostic performance to the multivariate models (Az 0.845-0.857). CONCLUSIONS: SUV max alone and multivariate models including SUV max are useful for the prediction of visceral pleural invasion by lung adenocarcinoma.

DOI： 10.1007/s12149-015-0999-x

Risk factors for systemic air embolism as a complication of percutaneous CT-guided lung biopsy: multicenter case-control study. Reviewed International journal

Hiroaki Ishii, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Hidefumi Mimura, Kotaro Yasui, Tetsuya Doke, Takashi Mukai, Hironori Kurokawa, Yoshitomo Ando, Soichiro Hase, Toshihiro Iguchi, Takayuki Yabuki, Kenichi Omae, Nobuhisa Tajiri, Toshiharu Mitsuhashi, Susumu Kanazawa

Cardiovascular and interventional radiology 37 ( 5 ) 1312 - 20 2014.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

PURPOSE: To determine risk factors for systemic air embolism by percutaneous computed tomography (CT)-guided lung biopsy. METHODS: This case-control study used data from 2216 percutaneous lung biopsy procedures performed over 11 years at 12 institutions in Japan. Systemic air embolism was identified by retrospective review of CT images obtained during and immediately after the procedures. To fulfill our objective, multiple variables were compared between cases and controls with univariate analyses by using Student's t test and Fisher's exact test for numerical and categorical values, respectively. Multivariate logistic regression analysis was then performed using selected variables. RESULTS: Ten cases of systemic air embolism and 2,206 controls were identified. Univariate analyses showed that the lesions in the lower lobe (P = 0.025) and occurrence of parenchymal hemorrhage (P = 0.019) were significant risk factors. Multivariate analysis showed that the use of a larger biopsy needle was a significant risk factor (P = 0.014). CONCLUSION: Parenchymal hemorrhage during the procedure, lesions in the lower lobe, and the use of larger biopsy needles may be risk factors for systemic air embolism by percutaneous CT-guided lung biopsy. Our findings may provide clues toward minimizing the risk of this complication.

DOI： 10.1007/s00270-013-0808-7

A simple example as a pedagogical device? Reviewed International journal

Etsuji Suzuki, Toshiharu Mitsuhashi, Toshihide Tsuda, Eiji Yamamoto

Annals of epidemiology 24 ( 7 ) 560 - 1 2014.7

Alternative definitions of "proportion eliminated". Reviewed International journal

Etsuji Suzuki, Toshiharu Mitsuhashi, Toshihide Tsuda, Eiji Yamamoto

Epidemiology (Cambridge, Mass.) 25 ( 2 ) 308 - 9 2014.3

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