Published papers

Background: Few data exist on long-term outcome in patients undergoing combined coronary CT angiography (CTA) and myocardial CT perfusion imaging (CTP) as well as invasive coronary angiography (ICA) and single photon emission tomography (SPECT). Methods: At 16 centers, 381 patients were followed for major adverse cardiac events (MACE) for the CORE320 study. All patients underwent coronary CTA, CTP, and SPECT before ICA within 60 days. Prognostic performance according binary results (normal/abnormal) was assessed by 5-year major cardiovascular events (MACE) free survival and area under the receiver-operating-characteristic curve (AUC). Results: Follow up beyond 2-years was available in 323 patients. MACE-free survival rate was greater among patients with normal combined CTA-CTP findings compared to ICA-SPECT: 85 vs. 80% (95% confidence interval [CI] for difference 0.1, 11.3) though event-free survival time was similar (4.54 vs. 4.37 years, 95% CI for difference: -0.03, 0.36). Abnormal results by combined CTA-CTP was associated with 3.83 years event-free survival vs. 3.66 years after abnormal combined ICA-SPECT (95% CI for difference: -0.05, 0.39). Predicting MACE by AUC also was similar: 65 vs. 65 (difference 0.1; 95% CI -4.6, 4.9). When MACE was restricted to cardiovascular death, myocardial infarction, or stroke, AUC for CTA-CTP was 71 vs. 60 by ICA-SPECT (difference 11.2; 95% CI -1.0, 19.7). Conclusions: Combined CTA-CTP evaluation yields at least equal 5-year prognostic information as combined ICA-SPECT assessment in patients presenting with suspected coronary artery disease. Noninvasive cardiac CT assessment may eliminate the need for diagnostic cardiac catheterization in many patients. Clinical trial registration: NCT00934037.

The recent appearance of multislice computed tomography (CT) has enabled noninvasive imaging of the coronary artery. Particularly, the appearance of 64-row CT has rapidly promoted its spread into routine medical practice. In this report, progress and current state of coronary CT employing multislice CT are outlined.

Background-Approaches for closing the left atrial appendage (LAA) have been developed for stroke prevention. However, the prevailing maneuvers require an open-chest surgery, intravascular access, or transseptal puncture. We evaluated the feasibility and safety of pericardial endoscopy-guided LAA ligation in a canine model. Methods and Results-We used a total of 8 canines and computed tomography was performed before the procedures. After a double percutaneous pericardiocentesis, a transurethral rigid endoscope was inserted into the pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by counter pulling the tip of the LAA with forceps. After confirming the positioning guided by transesophageal echocardiography, the ligature was securely tightened. Acute success was evaluated by transesophageal echocardiography and chronic success was evaluated by blood testing, computed tomography, and transesophageal echocardiography. The LAA ligation was safely achieved in all canines without major complications. One month after the ligation, the ligated LAA was replaced by fibrotic tissue, and both the transesophageal echocardiography and computed tomographic images revealed no residual shunt. There was only a localized adhesion of the pericardium, where the original LAA was located, without the need for antibiotic or steroid administration. The postprocedural internal surface of the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a slight elevation of the inflammatory markers, but this normalized spontaneously. Conclusions-Pericardial endoscopy-guided LAA ligation could provide an alternative, minimally invasive, and feasible solution for LAA closure that does not require vascular access or a transseptal puncture.

Objective To evaluate the effect of visceral obesity on surgical outcomes in laparoscopic radical prostatectomy (LRP). Methods Visceral fat area (VFA) and periprostatic fat area (PPFA) were used as index of visceral obesity. In addition to VFA and PPFA, age, body mass index (BMI), prostate weight, cross-section area of Retzius space, history of previous abdominal surgery, repeated transrectal needle biopsy, and neoadjuvant hormone therapy were recorded. LRP was separated into 7 steps (1: port insertion and lymph node dissection, 2: endopelvic fascia incision, 3: dorsal vein complex ligation, 4: prostate dissection from bladder neck, 5: dissection of seminal vesicle and vas deferens, 6: prostate dissection from rectum, and 7: vesicourethral anastomosis). Potential factors that prolonged total operative time (OT), pneumoperitoneum time, and duration of each step were assessed by multivariate logistic regression analysis. The association between visceral obesity and other surgical outcomes was also evaluated. Results One hundred sixteen LRPs were performed by a single experienced surgeon. High PPFA and prostate weight were independent factors that prolonged total OT and pneumoperitoneum time. High BMI was not a factor. PPFA affected steps 1, 4, 5, and 6, and prostate weight affected prolonged steps 5 and 6. Estimated blood loss, duration of urethral catheterization, postoperative hospital stay, perioperative complications, and margin status were not affected by visceral obesity. Conclusion PPFA was more useful to accurately predict prolonged OT than VFA or BMI. Safety and margin status were not compromised even in high PPFA group when operations were performed by an experienced surgeon. © 2013 Elsevier Inc. All Rights Reserved.

We report 5 patients with hemoptysis due to infectious pulmonary artery pseudoaneurysm (PAP) treated with endovascular embolization using N-butyl cyanoacrylate (NBCA) injected via bronchial and nonbronchial systemic arterial approaches. Infectious diseases included inactive tuberculosis (n = 3), nontuberculous mycobacteriosis (n = 1), and chronic infection of unknown origin (n = 1). Seven PAPs were detected on selective systemic angiography, and injection of NBCA was performed. Disappearance of all PAPs was confirmed on systemic arteriography after the intervention. In all patients, hemoptysis was stopped without major complications, and it did not recur during the follow-up period (mean, 351 d; range, 285-427 d).

Objective.: To examine the relationship between MRI structural damage and repair and plasma inflammatory cytokines in patients with RA. Methods.: A total of 88 newly diagnosed, untreated RA patients were enrolled. Contrast MRI of the dominant hand and X-rays of the hands and feet were performed at baseline and 1 year later. MR images were evaluated using RA MRI scoring, and X-ray. were assessed by the modified total Sharp score. Erosion progression was defined as changes in RA MRI scoring erosion or modified total Sharp score erosion of >0.5. Erosion repair was defined as erosion score changes of less than -0.5. Plasma levels of 10 cytokines were measured by electrochemiluminescence assay. Results.: Progression of bone erosion and repair were observed more frequently in MRI than in X-rays (erosion, 52% vs 26%, P < 0.001; repair, 26% vs 15%, P = 0.003, respectively). Baseline IL-6 levels and seropositivity were independent relevant factors for MRI erosion progression, with IL-6 having stronger effect than seropositivity. A receiver operating characteristic curve identified the baseline IL-6 level of 7.6 pg/ml for predicting erosion progression during 1 year, with an area under the curve of 0.82; higher IL-6 levels resulted in more erosion progression. Baseline low IL-6 was also an independent predictor for MRI erosion repair. Conclusion.: In newly diagnosed, untreated RA patients, baseline plasma IL-6 levels are responsible for 1-year MRI bone erosion progression and repair.

Objectives This study aimed to analyze the perioperative stroke rate, stroke lesions, outcome, risk factors, and stroke prevention following debranching with thoracic endovascular aortic repair (TEVAR). Design Retrospective study. Methods Between February 2011 and February 2015, 74 consecutive patients underwent debranching with TEVAR at our institution. Of these, the TEVAR proximal landing zone was “zone 0” in 23 patients, “zone 1” in 28, and “zone 2” in 23. Left subclavian artery (LSA) occlusion with coil embolization, balloon occlusion, or vascular plugging was performed in 27 patients. Mean follow-up time was 19.2 months (range 2–52 months). Results The in-hospital mortality rate was 4.1%. Stroke developed in 7 patients (9.5%), zone 0 in 4 patients, zone 1 in 2, and zone 2 in 1. Six of these patients had stroke lesions arising from the vertebral/basilar artery. Univariate analysis revealed a significant increase in the risk of postoperative stroke in patients with intraluminal atheroma (P = 0.001), those who underwent prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft (P = 0.002), and those with a long operative duration (P = 0.001). Additionally, LSA occlusion significantly decreased the incidence of stroke (P = 0.041). The postsurgical 1- and 2-year cumulative survival rates were 87.3% and 77.0%, respectively, in those without stroke, and 68.6% and 22.9%, respectively, in those with stroke (P = 0.012). Conclusions Stroke after debranching with TEVAR was associated with a high mortality. To prevent stroke, careful patient selection and protection of the vertebral artery are important. Prophylactic LSA occlusion at the time of stent-graft deployment might reduce the risk of perioperative stroke.

OBJECTIVES: To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC). PATIENTS AND METHODS: We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. RESULTS: Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. CONCLUSION: Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment.

© 2018 Objectives: To evaluate the usefulness of adding diffusion-weighted MRI (DW-MRI) to CT urography (CTU) for diagnosing upper tract urothelial carcinoma (UTUC). Materials and methods: We retrospectively evaluated 102 high-risk patients with UTUC who underwent both CTU and DW-MRI. The diagnostic performance of CTU and DW-MRI was evaluated in all the patients. Then, the diagnostic performance of DW-MRI in the patients with positive CTU findings was assessed based on the types of CTU findings (mass formation, wall thickening, and small filling defects). The diagnostic performance of DW-MRI and selective urine cytology sampling in these patients was also compared. Results: The sensitivity of DW-MRI (92%) was less than that of CTU (98%) (P = 0.25), since DW-MRI could not detect any small papillary tumors. The specificity of DW-MRI (91%) was greater than that of CTU (78%) (P = 0.065), since DW-MRI could discriminate some benign conditions from UTUC. Among the 59 positive CTU lesions, DW-MRI correctly diagnosed all 41 mass-forming lesions and improved the accuracy from 36% using CTU alone to 79% for 14 wall-thickening lesions but could not add any additional information for 4 small filling-defect lesions. Among the 44 patients with positive CTU findings who underwent selective urine cytology sampling, the sensitivity of DW-MRI (95%) was significantly greater than that of selective urine cytology sampling (56%) (P < 0.001). Conclusions: The addition of DW-MRI would be useful for both mass-forming and wall-thickening lesions. DW-MRI has the potential to reduce the frequency of selective urine cytology sampling for such lesions.

© 2019 The Author(s). Background: The magnitude of renal function recovery after kidney donation differs in donors with a heterogeneous background. Preoperative assessment of candidates with potentially unfavorable renal functional compensation is critical when baseline kidney function is marginal. We explored the significance of preserved kidney volume (PKV) and known preoperative risk factors for the prediction of unfavorable renal function compensation. Methods: We enrolled 101 living donors for whom a 1-mm sliced enhanced computed tomography scan was performed preoperatively and clinical data could be collected up to 1 year after donation. The donors whose estimated glomerular filtration rate (eGFR) at 1 year after donation was 70% or higher of baseline eGFR were assigned to the "favorable renal compensation" group and the others to the "unfavorable renal compensation" group. Results: Age, sex, and preoperative serum uric acid level were not significant predictors for "unfavorable renal compensation." Multivariable logistic regression analysis revealed that body mass index (BMI) and body surface area (BSA)-adjusted PKV were independent preoperative risk factors for "unfavorable renal compensation" (adjusted odds ratio, 1.342 and 0.929, respectively). Hypertension and preoperative eGFR were not independent predictors when adjusted with BMI and BSA-adjusted PKV. Receiver operative characteristic analysis revealed that the predictive equation with the two independent predictors yielded a good accuracy to detect donor candidates with unfavorable renal functional compensation (area under the curve = 0.803), and the optimal cut-off values were identified as 23.4 kg/m 2 for BMI and 107.3 cm 3 /m 2 for BSA-adjusted PKV. Conclusions: BMI and BSA-adjusted PKV may be useful to select candidates with potentially unfavorable renal function compensation before kidney donation.

© 2017 Elsevier Inc. Introduction Heat-denatured 99mTc-labeled red blood cells (RBCs) are used for detecting splenic tissues with scintigraphy. The present study aimed to evaluate the feasibility of using heat-denatured [18F]fluorodeoxyglucose ([18F]FDG)-labeled RBCs in detecting splenic tissues using positron emission tomography (PET) in rats. Methods RBCs were washed with phosphate buffered saline, labeled with [18F]FDG at 38°C, and heat-denatured at 50°C for 15 min. In vitro stability was assessed by measuring extracellular radioactivity during the 0–180 min incubation at 37°C. Thin layer chromatography (TLC) of the extracellular fluid was performed. The autologous RBCs were intravenously injected in four rats and PET scanning was simultaneously performed for 30 min. Time-activity curves of several organs, including the spleen, were analyzed on the PET images. Results Labeling efficiency was 92%. Low levels of radioactivity were released from the labeled RBCs for 180 min. TLC revealed that 80% of the released radioactivity was due to [18F]FDG-6-phosphate. Whole body images showed strong uptake of heat-denatured [18F]FDG-labeled RBCs in the spleen soon after injection in all four rats. Time-activity curves revealed that the splenic uptake continued to increase for 30 min and the amount of radioactivity in the other organs, except the urinary bladder, decreased after the initial surge. Conclusions Heat-denatured [18F]FDG-labeled RBCs are suitable spleen-specific agents for PET. This method is clinically relevant as an alternative for heat-denatured 99mTc-labeled RBC scintigraphy.

© 2019, Springer Nature America, Inc. Background: Tumor contact length (TCL) is defined as the extent of contact between prostate cancer and the prostatic capsule, and its predictive value for microscopic extraprostatic extension (EPE) has been reported. However, the impact of the zonal origin (anterior or posterior tumor) of the tumor on the diagnosis of EPE is controversial. Methods: We retrospectively analyzed the records of 233 consecutive patients who underwent preoperative MRI and radical prostatectomy. We designated their tumors as anterior or posterior, and evaluated the correlation between the TCL measured by MRI and microscopic EPE in the radical prostatectomy specimen. Then, we created the predicted probability curves for EPE versus TCL for anterior and posterior prostate cancer. Results: There were 109 patients (47%) with an anterior tumor and 124 patients (53%) with a posterior tumor. Postoperative pathological analysis confirmed pT3 in 18 patients (17%) with an anterior tumor and in 53 patients (43%) with a posterior tumor. Multivariate analysis demonstrated that the zonal origin of the tumor was an independent predictive factor for EPE. We developed separate probability curves of EPE versus TCL for anterior and posterior prostate cancer, which revealed that anterior tumors were less likely to invade the extraprostatic tissues. Among patients whose TCL was 10–20 mm, 9/32 patients (28%) with an anterior tumor had EPE compared with 24/45 patients (53%) with a posterior tumor (p = 0.036). The decision curve of this EPE predictive model had high clinical efficacy. Conclusions: Our results indicate that anterior tumors have more favorable pathological characteristics than posterior tumors with the same TCL measured by MRI. We constructed two separate predicted probability curves for EPE after discriminating anterior and posterior tumors, which will be useful for decision making in clinical practice.

© 2019 Elsevier Ltd Chronic subdural hematoma (CSDH) is a common disease in older individuals with a substantial rate of recurrence. The mechanism of CSDH recurrence remains unclear. This study aimed to detect imaging parameters that could indicate the risk for CSDH recurrence by using quantitative volumetric analysis and computed tomography (CT) texture analysis (CTTA). Clinical and imaging parameters were retrospectively investigated in 147 newly diagnosed CSDH lesions in 114 patients surgically treated at the Keio University Hospital during a 6-year period. For CT images, quantitative volumetric and texture analyses were performed. Hematoma volume, postoperative air volume, hematoma density, and texture parameters including kurtosis, skewness, and entropy were evaluated and compared with CSDH recurrence rate. Data were statistically evaluated, and a difference of p < 0.05 was considered significant. Reoperation for CSDH recurrence was required in 27 sides (18.4%) of 26 patients. Multivariate analysis showed that postoperative hematoma volume and postoperative hematoma density were independent risk factors for symptomatic CSDH recurrence that required reoperation. Postoperative hematoma volume, postoperative significant residual air, and postoperative hematoma density were also identified as independent risk factors for potential CSDH recurrence. Preoperative hematoma entropy was prone to be associated with both symptomatic and potential CSDH recurrence in univariate analysis, but not in multivariate analysis because of confounding factors. Quantitative volumetric analysis and CTTA could aid in distinguishing individuals at risk for CSDH recurrence.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. The promoter methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene has been described as the most important predictor of chemotherapeutic response and patients’ survival in glioblastomas (GBs). Therefore, prediction of the MGMT promoter methylation status by imaging would help to preoperatively decide the overall treatment strategy as well as surgical strategy. This study aimed to detect imaging parameters to predict MGMT promoter methylation in GBs by using a commercially available software. We investigated three imaging features (ring enhancement, tumor location, and laterality) and apparent diffusion coefficient (ADC) parameters in 48 newly diagnosed GBs treated at Keio University Hospital in 2006 or later. For ADC, texture analyses were performed. Regions of interest (ROIs) were drawn manually with reference to contrast-enhanced areas, excluding necrotic and cystic regions. Mean ADC value and ADC histogram parameters, including kurtosis, skewness, and entropy, were compared with MGMT promoter methylation. Each parameter was evaluated to determine correlation with MGMT promoter methylation, and the parameters with significant associations with the methylation status were correlated with the MGMT-positive cell ratio determined by immunohistochemistry (IHC) analysis. The mean ADC value and ADC entropy were significantly associated with MGMT promoter methylation. The combination of mean ADC value and ADC entropy predicted MGMT promoter methylation, with a PPV of 81.2% and specificity of 88.9%. The mean ADC value and ADC entropy were negatively correlated with the MGMT-positive cell ratio in the IHC analysis. This study demonstrated that texture analyses of ADC histograms in GBs were predictive of MGMT promoter methylation.

Background: Because cancers of hollow organs such as the esophagus are hard to detect even by the expert physician, it is important to establish diagnostic systems to support physicians and increase the accuracy of diagnosis. In recent years, deep learning-based artificial intelligence (AI) technology has been employed for medical image recognition. However, no optimal CT diagnostic system employing deep learning technology has been attempted and established for esophageal cancer so far. Purpose: To establish an AI-based diagnostic system for esophageal cancer from CT images. Materials and methods: In this single-center, retrospective cohort study, 457 patients with primary esophageal cancer referred to our division between 2005 and 2018 were enrolled. We fine-tuned VGG16, an image recognition model of deep learning convolutional neural network (CNN), for the detection of esophageal cancer. We evaluated the diagnostic accuracy of the CNN using a test data set including 46 cancerous CT images and 100 non-cancerous images and compared it to that of two radiologists. Results: Pre-treatment esophageal cancer stages of the patients included in the test data set were clinical T1 (12 patients), clinical T2 (9 patients), clinical T3 (20 patients), and clinical T4 (5 patients). The CNN-based system showed a diagnostic accuracy of 84.2%, F value of 0.742, sensitivity of 71.7%, and specificity of 90.0%. Conclusions: Our AI-based diagnostic system succeeded in detecting esophageal cancer with high accuracy. More training with vast datasets collected from multiples centers would lead to even higher diagnostic accuracy and aid better decision making.

Objective: Photoacoustic imaging is a new technique that can evaluate the vascular system using photoacoustic effects. The present study compared the ability of the new photoacoustic lymphangiography (PAL) method and more standard near-infrared fluorescence (NIRF) to image the lymphatic system in patients with secondary lymphedema after gynecological cancer surgery. Methods: Patients with secondary lymphedema in the lower extremities after gynecologic cancer surgery, who were assessed using PAL between May 2018 and January 2019, were recruited. NIRF was performed first using 5.0 mg/mL of indocyanine green injected using a 0.2-cc 30-gauge needle. Correlations between NIRF and PAL findings on patient images were subsequently examined. Results: Seventeen patients with secondary lymphedema were enrolled. The mean age of the patients was 61 ± 11 years. The imaging sites were the medial lower leg in 15 patients, the posterior lower leg in 9 patients, the lateral lower leg in 7 patients, the medial knee in 4 patients, and other areas in 3 patients. A total of 38 pictures were obtained. Five distinct lymphatic patterns were observed over the entire sample using PAL: straight, winding, spiderweb, nebulous, and black-out pattern. Eighteen of the 24 limbs (75%) that exhibited a linear pattern in NIRF exhibited a straight pattern in PAL, and 19 of the 20 limbs (95%) that exhibited a splash pattern in NIRF exhibited a winding or spiderweb pattern in PAL. Eight limbs exhibiting diffuse patterns without linear or splash patterns with NIRF were all nebulous or black-out patterns in PAL. This suggests that more severe lymphatic degeneration was associated with poorer visualization in PAL. Conclusions: NIRF plays an important role in lymphedema treatment. In the present study, various PAL patterns were compared with those observed using NIRF. PAL provided clearer images including transectional views, which were not available using NIRF, and may promote further understanding of the changes in the lymphatic structure and function in patients with secondary lymphedema.