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To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child–Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%. [Display omitted] [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the impact of functional and anatomic complete revascularization on long-term clinical outcomes after coronary artery bypass grafting (CABG). Of 2034 patients who underwent primary isolated CABG between 2006 and 2017, 1162 patients who underwent off-pump CABG for 3-vessel disease and for whom data on functional and anatomic completeness of revascularization were available on the basis of preoperative myocardial single photon emission computed tomography and early postoperative graft angiography were enrolled. The median follow-up duration was 82.4 months (interquartile range, 50.8-122.4 months). Univariate and multivariate analyses were performed to evaluate the impact of the functional and anatomic completeness of revascularization on long-term survival. Of 1162 patients, anatomic complete revascularization was achieved in 1014 patients (87.3%), whereas functional complete revascularization was achieved in 1077 patients (92.7%). Early mortality occurred in 7 patients. Late death occurred in 322 of 1155 early survivors. The 5- and 10-year overall survival rates were 84.3% and 66.7%, respectively. Univariate analyses demonstrated that functional completeness of revascularization was a statistically significant risk factor (P =.038), whereas anatomic completeness was not (P =.859). The multivariate analysis showed that functional completeness of revascularization (hazard ratio, 1.54; 95% CI, 1.08-2.22; P =.019) and age, underweight status, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, and left ventricular dysfunction were significant factors associated with long-term survival. Functional rather than anatomic completeness of revascularization has a significant impact on the long-term survival in patients who undergo CABG. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs. Methods: 39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively. Results: Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant. Conclusions: Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve. [ABSTRACT FROM AUTHOR]

Purpose: To address the feasibility of infusion of yttrium-90 (90Y) glass microspheres directly through the right inferior phrenic artery (RIPA).Materials and Methods: From November 2015 to May 2017, 20 patients underwent 90Y radioembolization through the RIPA. When the systemic-to-pulmonary shunt was demonstrated on C-arm computed tomography (CT) of the RIPA, prophylactic embolization by polyvinyl alcohol (PVA) particles was performed prior to infusion of 90Y glass microspheres. Follow-up CT scans were retrospectively reviewed for pulmonary complications. Tumor response was determined by the modified Response Evaluation Criteria in Solid Tumors.Results: Nine (45%) patients had systemic-to-pulmonary shunts on C-arm CT images of the RIPA. The feeder of the systemic-to-pulmonary shunt was the azygoesophageal branch (n = 7) and the anterior branch (n = 2). The mean activity of 90Y glass microspheres infused into the RIPA was 0.49 GBq (range, 0.19-1.55 GBq). No patient had symptomatic radiation pneumonitis or cutaneous complications during follow-up. Seven patients had focal atelectasis (n = 5), focal ground-glass opacity (n = 2), and/or a small amount of pleural effusion (n = 2) on follow-up image. Best tumor response fed by the RIPA was complete response (n = 4), partial response (n = 9), stable disease (n = 2), progressive disease (n = 4), and unevaluable (n = 1).Conclusion: The administration of 90Y glass microspheres through the RIPA may be safe after embolization of a systemic-to-pulmonary shunt identified on C-arm CT. [ABSTRACT FROM AUTHOR]

Objectives The authors sought to compare the diagnostic performance of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and resting distal coronary artery pressure/aortic pressure (Pd/Pa) using 13 N-ammonia positron emission tomography (PET). Background The diagnostic performance of invasive physiological indices was reported to be different according to the reference to define the presence of myocardial ischemia. Methods A total of 115 consecutive patients with left anterior descending artery stenosis who underwent both 13 N-ammonia PET and invasive physiological measurement were included. Optimal cutoff values and diagnostic performance of FFR, iFR, and resting Pd/Pa were assessed using PET-derived coronary flow reserve (CFR) and relative flow reserve (RFR) as references. To compare discrimination and reclassification ability, each index was compared with integrated discrimination improvement (IDI) and category-free net reclassification index (NRI). Results All invasive physiological indices correlated with CFR and RFR (all p values <0.001). The overall diagnostic accuracies of FFR, iFR, and resting Pd/Pa were not different for CFR <2.0 (FFR 69.6%, iFR 73.9%, and resting Pd/Pa 70.4%) and RFR <0.75 (FFR 73.9%, iFR 71.3%, and resting Pd/Pa 74.8%). Discrimination and reclassification abilities of invasive physiological indices were comparable for CFR. For RFR, FFR showed better discrimination and reclassification ability than resting indices (IDI = 0.170 and category-free NRI = 0.971 for iFR; IDI = 0.183 and category-free NRI = 1.058 for resting Pd/Pa; all p values <0.001). Conclusions The diagnostic performance of invasive physiological indices showed no differences in the prediction of myocardial ischemia defined by CFR. Using RFR as a reference, FFR showed a better discrimination and reclassification ability than resting indices. [ABSTRACT FROM AUTHOR]

Background Improvements in myocardial perfusion and thickening were compared in coronary artery bypass grafting patients who received saphenous vein (SV) Y-composite grafts versus those who received right internal thoracic artery ([R]ITA) Y-composite grafts. Methods Of the 224 patients enrolled in a randomized clinical trial, 116 patients (SV group, n = 65; RITA group, n = 51) in whom myocardial single-photon–emission computed tomography was performed preoperatively, and at 3 months and 1 year postoperatively, were retrospectively studied. A 20-segment model was adopted, and a total of 792 ischemic myocardial segments (SV group, n = 443; RITA group, n = 349) were analyzed. The reversibility score (rest minus stress perfusion value) as an indicator of ischemic myocardium, and Z-values for segmental myocardial thickening, were calculated. Results Compared with preoperative values, both myocardial perfusion and segmental myocardial thickening had improved significantly at 3 months and 1 year postoperatively (reversibility scores [mean ± SD] were, respectively: 13.5 ± 8.0 vs 5.8 ± 6.2 and 5.1 ± 6.2, P < .001; Z-values were −1.13 ± 1.53 vs −0.62 ± 1.40 and −0.67 ± 1.35, P < .001). Mixed-effect model analyses showed no differences in improvements in myocardial perfusion and segmental myocardial thickening between the 2 groups 1 year after revascularization. Separate analysis demonstrated less improvement of myocardial perfusion in the right coronary artery territory of the RITA group than the SV group, with marginal significance ( P = .056). Conclusions Improvements in myocardial perfusion and segmental myocardial thickening were similar between the 2 groups at 1 year after revascularization. The SV, versus the right ITA, composite graft may be more beneficial in perfusion improvement of the right coronary artery territory. [ABSTRACT FROM AUTHOR]

Objectives This study sought to investigate the efficacy of 11 C-Pittsburgh B (PiB) positron emission tomography (PET)/computed tomography (CT) in the diagnosis of cardiac amyloidosis. Background The PiB compound has been promising for detection of amyloid deposits in the brain. Methods A total of 22 consecutive patients were enrolled in this prospective pilot study of monoclonal gammopathy patients with suspected cardiac amyloidosis. The study consisted of a series of 11 C-PiB PET/CT, echocardiography, cardiac magnetic resonance, and endomyocardial biopsy within a 1-month period. In addition, 10 normal subjects were recruited to determine the most optimal cut-off value for a positive 11 C-PiB PET/CT scan. Results Among the 22 patients, 15 patients were diagnosed as cardiac amyloidosis by endomyocardial biopsy and 5 patients had undergone chemotherapy previously before the 11 C-PiB PET/CT. There were no differences in echocardiographic parameters between patients with versus without cardiac amyloidosis, except for a marginal difference in the left ventricular end-diastolic dimension (median 41.0 mm [range 33.0 to 49.0 mm] vs. 50.0 mm [range 38.0 to 55.0 mm], p = 0.066). 11 C-PiB PET/CT was positive in 13 of 15 biopsy-proven cardiac amyloidosis patients, whereas none of the patients without cardiac amyloidosis demonstrated positive 11 C-PiB PET/CT scan results. The maximal myocardium-to-blood cavity ratio was significantly different between patients with versus without cardiac amyloidosis (median 3.9 [range 1.7 to 19.9] vs. 1.0 [range 0.8 to 1.2], p < 0.001). In association with the significant difference of 11 C-PiB uptake in the myocardium between the chemotherapy naïve versus the previous chemotherapy group (median 10.4 [range 1.7 to 19.9] vs. 2.3 [range 1.7 to 3.8], p = 0.014), all except 1 patient among the 5 previously treated patients had responded to chemotherapy by serum free light chain assay results at the time of 11 C-PiB PET/CT scan. Conclusions 11 C-PiB PET/CT may be valuable for the diagnosis of cardiac amyloidosis noninvasively. Whether 11 C-PiB PET/CT may be a good surrogate marker of active light chain deposition in the myocardium warrants further investigation in a larger number of patients. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether arterioportal shunting to the contralateral lobe attenuates liver function and hypertrophy of the nontargeted liver after radioembolization in patients with hepatocellular carcinoma (HCC).Materials and Methods: The current retrospective study included 46 patients who received radioembolization for HCC contained within the right lobe between 2012 and 2020. The patients were divided into the following groups on the basis of the presence and extent of arterioportal shunting: patients with retrograde arterioportal shunting to the left lobe (contralateral group) and patients with arterioportal shunt limited to the right lobe or no arterioportal shunt (control group). Safety profiles, including adverse events, tumor response, and overall survival, were compared. With the volume of the left lateral segment used as a surrogate marker for nontarget liver, the degree of hypertrophy was compared between the 2 groups at 3 and 6 months.Results: Liver function significantly deteriorated in the contralateral group in a month (P ≤ .05). Tumor response and overall survival did not significantly differ between the 2 groups. The degree of hypertrophy was significantly higher in the control group than in the contralateral group at 3 months (10.6% vs 3.5%; P = .008) and 6 months (20.7% vs 2.4%; P < .001).Conclusions: In patients with arterioportal shunting to the contralateral lobe, hypertrophy of the nontarget liver may not occur and the liver function may be worsened. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation. Methods: Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively. ALK fluorescence in situ hybridization and EGFR mutations were tested. Maximum standardized uptake value (SUVmax) and metastatic characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status. Results: Of the 331 lung adenocarcinoma patients, 18 were ALK positive (ALK+), 156 were EGFR mutation positive (EGFR+), and 157 were wild type (WT) for both ALK and EGFR mutation. The ALK+ tumor showed significantly higher SUVmax and more common metastasis to lymph nodes and distant organs than those of other genotypes in overall patients (P <0.01). In a subgroup analysis of advanced stage (stage IIIb and IV), ALK+ lung cancer showed significantly higher SUVmax (P <0.05) than EGFR+ tumors. In another subgroup analysis of size matched groups, ALK+ tumors showed significant difference in SUVmax, lymph node and distant metastasis (P <0.01), particularly in the moderate-sized tumors (1.5–3cm). Conclusion: ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and more rapid metastasis to lymph nodes or distant sites compared with those with EGFR mutation and wild type, which suggests more aggressive features of ALK rearrangement. [Copyright &y& Elsevier]

Background: We evaluated the effect of isolated off-pump coronary artery bypass grafting on functional ischemic mitral regurgitation (IMR) associated with acute coronary syndrome. Methods: Of 1,419 acute coronary syndrome patients who underwent coronary revascularization between 2000 and 2010 (1,324 off-pump and 95 on-pump), 59 OPCAB patients had greater than mild degree functional IMR preoperatively (31 mild to moderate, 23 moderate, 5 severe). Clinical outcomes and results from echocardiography, angiography, and myocardial single-photon emission computed tomography performed early and 1 year postoperatively were analyzed. Results: Operative mortality was 5.1% (3 of 59). All survivors underwent early postoperative echocardiograms, which showed 0 patients with worsened IMR; 41 with less than or equal to mild degree residual IMR (NMR group); and 15 with greater than mild degree IMR (RMR group). Myocardial single-photon emission computed tomography revealed that RMR patients had more reversible ischemic myocardial segments preoperatively than NMR patients (p = 0.009). Successful right coronary revascularization with proven graft patency was a predictor of early improvement of IMR (p = 0.024). There were no differences in postoperative morbidities between the 2 groups. One-year follow-up echocardiograms demonstrated further improvement in 10 of 13 RMR patients. No patients experienced mitral valve-related events during follow-up. Overall survival and major adverse cardiac event-free survival rates at 5 years were 84.6% and 78.1%, respectively, with no intergroup differences. Conclusions: Most functional IMR associated with acute coronary syndrome, including severe degree IMR, improved during the first postoperative year after off-pump coronary artery bypass grafting. [ABSTRACT FROM AUTHOR]

Abstract: Positron emission mammography (PEM) has been reported to have higher sensitivity than whole-body positron emission tomography (PET)due to higher spatial resolution. However, no direct evidence exists regarding the imaging sensitivity of PEM related to lesion size. In the present study, imaging sensitivity of PEM was investigated in relation to pathologically confirmed tumor size. A total of 113 breast lesions from 101 patients were included in the analysis. The patients underwent 18F-fluorodeoxyglucose (FDG) PEM and whole-body PET/computed tomography (CT) before surgical resection, and images were analyzed visually and quantitatively using the tumor-to-normal-tissue uptake ratio (TNR). Tumors were classified into four groups based on size using pathologic results, and sensitivities of PEM and PET/CT were compared in the overall subjects and in each size group. In visual analysis, PEM showed significantly higher imaging sensitivity than PET/CT (95% vs. 87%; P = 0.004), which was more definite in the small-tumor groups. In quantitative analysis, the TNR of PEM was significantly higher than that of PET/CT in the small-tumor groups, whereas no difference was found in the overall group. With a cutoff TNR of 2.5, PEM showed significantly higher sensitivity than PET/CT in the overall and small-tumor groups. In conclusion, PEM had higher imaging sensitivity than PET/CT, particularly in small tumors. The results suggest that PEM may be used for diagnosis and characterization of small lesions as a supplementary imaging modality for PET/CT. [Copyright &y& Elsevier]

Background: Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RoT) has good postoperative and excellent cosmetic outcomes. To assess the surgical completeness of BABA RoT, it was compared to open thyroidectomy (OT) after propensity score matching of the cohorts. Methods: Between 2008 and 2010, 760 patients who underwent total thyroidectomy with central node dissection (CND) caused by papillary thyroid carcinoma (PTC) in Seoul National University Hospital were enrolled; 327 BABA robotic and 423 open method operations were performed. We selected 174 robotic and 237 open thyroidectomy patients who received radioactive iodine (RAI) ablation. Propensity score matching using 3 demographic and 5 pathologic factors was used to generate 2 matched cohorts, each composed of 108 patients. Results: The matched BABA RoT and OT cohorts were not different with regard to the RAI uptake ratio, stimulated thyroglobulin (Tg) levels, or proportion of patients with stimulated Tg levels <1.0 ng/mL on the first ablation. The number of RAI ablation sessions and RAI doses needed to achieve a complete ablation also did not differ significantly. Conclusion: The surgical completeness of BABA RoT did not differ from OT. BABA RoT may be suitable for patients with PTC who prefer scarless neck surgery. [Copyright &y& Elsevier]

Background: Late improvements in myocardial perfusion and thickening after off-pump revascularization were evaluated during a 5-year follow-up by myocardial single photon emission computed tomography. Methods: Between 2001 and 2003, 68 patients who underwent off-pump coronary artery bypass grafting using bilateral internal thoracic artery Y-composite (group Y, n = 41) or in situ (group I, n = 27) grafts for revascularization of the left coronary artery territory were enrolled. Myocardial single photon emission computed tomography was performed preoperatively and at 3 months, 1 year, and 5 years postoperatively. A 20-segment model was adopted. As an indicator of ischemic myocardium, the reversibility score was defined as a measure of rest minus stress perfusion values. A total of 374 segments that showed a reversibility score of ≥7 preoperatively were included. Z values for thickening were calculated as observed values minus reference values divided by the reference standard deviation. Mixed-model analysis was used to compare the two groups with respect to the time sequences of myocardial reversibility scores and Z values. Results: Postoperative reversibility scores improved significantly at 3 months (p < 0.001) and further at 5 years (p = 0.030). Postoperative Z values improved significantly at 3 months (p < 0.001), between 1 year and 5 years (p = 0.006), and further at 5 years (p = 0.004). In the mixed models, there were no significant differences in reversibility scores and Z values between groups Y and I at any point. Conclusions: Reversibility scores and thickening gradually improved during 5 years after off-pump revascularization using bilateral internal thoracic arteries. No significant differences were observed between Y-composite and bilateral in situ grafts in terms of reversibility score and thickening improvement at 5 years postoperatively. [Copyright &y& Elsevier]

PURPOSE: To evaluate the antitumor effect of transcatheter arterial embolization (TAE) with use of rhenium 188 HDD (4-hexadecyl 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol)–labeled iodized oil and to compare it with that of transcatheter arterial chemoembolization (TACE) with use of an established chemotherapeutic agent and iodized oil in experimentally induced liver tumor. MATERIALS AND METHODS: VX2 carcinoma was grown in the livers of 57 rabbits. TAE was performed with 188Re-HDD–labeled iodized oil (Re-Lp group; n = 21), doxorubicin/iodized oil emulsion (Dx-Lp group; n = 21), and iodized oil alone (n = 15). Sequential conjugated planar imaging was performed for dosimetry of the radioisotope in the Re-Lp group (n = 15). Growth ratio and percentage of viable tumor were estimated by computed tomography and histopathologic examination. Hepatic and hematologic toxicities were evaluated by biochemical analysis. RESULTS: On conjugated planar imaging, radioactivity was concentrated on the tumor (effective half-life, 16.2 hours), and mean radiation dose to the tumor was 147.7 Gy. The mean growth ratios 1, 2, and 3 weeks after TAE and the percentage of viable tumor in the Re-Lp group (−3.4, −7.6, −11.1, and 0.3%) and the Dx-Lp group (−3.2, −5.3, 29.0, and 2.6%) were significantly lower than the respective values in the iodized oil group (45.5, 145.4, 283.0, and 30.1%; P <.001). However, the differences between the values in the Re-Lp group and those in the Dx-Lp group were not significant (P values of .165–0.497 for growth ratios; P = .134 for percentage of viable tumor). There was similar transient hepatotoxicity in all three groups. CONCLUSION: TAE with 188Re-HDD–labeled iodized oil has potent antitumor effect in VX2 liver tumor that is comparable with that of TACE with an established chemotherapeutic agent. [Copyright &y& Elsevier]

Background: To optimize the use of thallium 201 rest-redistribution study in Tl-201/technetium 99m sestamibi dual-isotope single photon emission computed tomography (SPECT), the predictability of Tl-201 rest-redistribution for viable myocardium was examined according to the degree of perfusion reserve.Methods and Results: Twenty patients with both unstable angina and left ventricular dysfunction were enrolled. Tl-201 rest-dipyridamole stress Tc-99m sestamibi gated SPECT/Tl-201 24-hour redistribution SPECT was performed before and 3 months after coronary artery bypass grafting. Through use of a 20-segment model, segmental stress perfusion, rest perfusion, and systolic thickening were quantified on gated SPECT by means of automatic quantitation software. Perfusion was expressed as the average percentage of maximal radioactivity uptake. To represent perfusion reserve, the perfusion difference score (PDS) was defined as rest perfusion minus stress perfusion. A low PDS indicated little or no inducible ischemia, and a high PDS indicated inducible ischemia. In dysfunctional myocardium, viability was defined by the improvement of thickening after coronary artery bypass grafting. The overall predictability of Tl-201 redistribution for viability was 0.709 of the area under the curve (AUC) in receiver operating characteristic analysis. With a cutoff of 7, predictability was significantly better in the low PDS group (AUC = 0.785) than in the high PDS group (AUC = 0.582).Conclusions: The predictability of Tl-201 rest-redistribution for viability differs according to perfusion reserve. It was more reliable for dysfunctional myocardium with persistent perfusion decrease. On the basis of the continuum hypothesis of chronic stunning and hibernation, we suggest that dysfunctional myocardium with persistent perfusion decrease should be assessed by Tl-201 redistribution SPECT. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate graft patency rates during the 5 years after coronary artery bypass grafting according to the functional significance of the coronary artery stenosis, as determined by myocardial single-photon-emission computed tomography. Two hundred ninety-five patients who underwent coronary artery bypass grafting using Y-composite grafts based on the in situ left internal thoracic artery, and in whom preoperative stress/rest myocardial single-photon-emission computed tomography and 1-year angiographies were available were enrolled. Seven hundred sixty-nine and 262 distal anastomoses were constructed to ischemic and nonischemic areas, respectively. One-year and 5-year angiographic occlusion rates were evaluated in all and 80.3% of study patients, respectively. Factors associated with graft occlusion were evaluated using generalized linear mixed-effects models. Overall 1- and 5-year graft occlusion rates were 4.3% (44 of 1031 distal anastomoses) and 5.5% (45 out of 820), respectively. The occlusion rates of grafts bypassed to vessels with functionally significant and insignificant stenosis were 2.7% (21 out of 769) and 8.8% (23 out of 262) at 1 year and were 4.0% (25 out of 618) and 9.9% (20 out of 202) at 5 years, respectively. Graft occlusion during the 5 years after coronary artery bypass grafting was associated with the functional significance of coronary artery stenosis (odds ratio, 0.50; 95% confidence interval, 0.28-0.92). The odds ratio of the graft occlusion according to functional ischemia was lower and significant in grafts to arteries with intermediate stenosis (stenosis ≥70% but <90%; odds ratio, 0.34; 95% confidence interval, 0.13-0.93) whereas it was higher and insignificant in grafts to arteries with severe stenosis (≥90% stenosis; odds ratio, 0.76; 95% confidence interval, 0.33-1.72). Graft occlusion during the 5 years after coronary artery bypass grafting was associated with the functional significance of coronary artery stenosis, particularly when the stenosis degree was not severe. [ABSTRACT FROM AUTHOR]

• Standardized uptake value is prognostic in the current lung cancer staging system. • Maximum standardize uptake value can be used in a continuous or a categorized form. • Standardize uptake value can be used to up- or downstage the clinical T category. This retrospective cohort study aimed to analyze the prognostic effect of maximum standardized uptake value (SUVmax) as a complementary T factor in addition to the clinical T category of the eighth-edition staging system for the prediction of disease-free survival (DFS) in patients with resected lung adenocarcinomas. A total of 572 patients (male:female = 235:337; median age, 64 years) with clinical stage I (T1-T2aN0M0) adenocarcinomas underwent preoperative fluorine-18 fluorodeoxyglucose positron emission tomography and subsequent lobectomy between 2009 and 2015. The prognostic values of SUVmax and PET T category [categorized SUVmax; PET T1 (SUVmax ≤2), PET T2 (2< SUVmax ≤7), and PET T3 (SUVmax >7)] in conjunction with the clinical T category were analyzed using a multivariable Cox regression and a likelihood-ratio test, respectively. The clinical T category was then upstaged or downstaged (cT Modified) based on PET T. This new categorization system was evaluated using a Cox regression and then compared with the clinical T category. Multivariable-adjusted Cox regression revealed that SUVmax and PET T were independent and significant predictors with the current clinical T category for DFS. Regarding SUVmax, the adjusted hazard ratio (HR) was 1.048 (95% CI: 1.009, 1.089; P = 0.017). Regarding PET T, the adjusted HRs were 2.365 (95% CI: 1.034, 5.406; P = 0.041) in PET T2 and 3.005 (95% CI: 1.258, 7.179; P = 0.013) in PET T3. The inclusion of the PET-derived factors substantially improved the model fit (P < 0.05). cT Modified was a significant predictor of DFS, which improved the prognostic discrimination of lung adenocarcinomas. SUVmax and PET T are independent prognostic factors after adjustment for the clinical T category. The PET T category could be used to adjust the clinical T category preoperatively. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT. [Copyright &y& Elsevier]

[Display omitted] • Non-peptide-guided secretion of anti-HER2 scFv was attempted in E. coli. • The MBP-fused scFv was effective for the chemical-aided extracellular secretion. • The MBP-scFv was simply purified and retained the target-binding affinity. • Enzymatic cleavage of the MBP-scFv by TEV protease yielded the isolated scFv. • Specific binding of the final scFv product to HER2 showed a Kd value of 0.2 nM. The overexpression of human epidermal growth factor receptor 2 (HER2) is recognized as a hallmark of several solid tumors, and the anti-HER2 monoclonal antibody and its engineered variants have been developed as therapeutic or diagnostic tools for HER2-overexpressing cancers. Here, we demonstrate the first example of extracellular production of an anti-HER2 single-chain variable fragment (scFv) in Escherichia coli via a non-peptide-guided secretion. The initial construct expressing an engineered green fluorescent protein-fused scFv was successful in extracellular secretion, but the expressed protein appeared to be readily truncated before the final purification. Alternatively, by adding Triton X-100 to the culture media, maltose-binding protein (MBP)-fused scFv could be secreted without significant truncation, and homogeneous purification of the intact protein was enabled. The affinity of the MBP-fused scFv to the extracellular domain of HER2 was confirmed by enzyme-linked immunosorbent assay, and the dissociation constant of the finally isolated scFv estimated by surface plasmon resonance was approximately 0.2 nM, which was superior to the other known anti-HER2 scFvs. Given that anti-HER2 scFv is an invaluable asset for developing various therapeutic or diagnostic agents for cancers, we expect that our method for the extracellular production will enable a better manufacturing process for its industrial application. [ABSTRACT FROM AUTHOR]

Background: It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.Objectives: The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.Methods: This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.Results: The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).Conclusions: These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients. [ABSTRACT FROM AUTHOR]

Cetuximab is a murine-human chimeric monoclonal antibody (mAb) that is clinically used to treat epidermal growth factor receptor (EGFR)-positive cancers. As antibody fragment engineering has emerged as an economic alternative to mAb drugs via bacterial production, we have previously generated FM318, a recombinant Fab adopted from cetuximab. Here, in an effort to facilitate industrial development, we searched for useful mutations that could increase its production yields. Amino acid substitutions were selected to resemble the humanized sequence to avoid unexpectedly raising immunogenic problems by the mutations. As a result, FM329, which accommodates L3Q/L4 M mutations in the light chain and S15G/Q16G in the heavy chain Fd, showed a high production yield in a fed-batch operation, reaching approximately 3.5 times FM318 productivity, with its structure and EGFR-binding affinity being maintained. Additionally, for a potential application to antibody-drug conjugates, a cytotoxic agent, DM1 was successfully linked to FM329 with an average drug-to-antibody ratio of 1.4. The conjugate showed dramatically increased anticancer activity with retention of EGFR-binding affinity. Collectively, we suggest that the partially humanized recombinant cetuximab Fab, FM329, and its DM1 conjugate would serve as promising platforms to develop an economic alternative to cetuximab and/or an improved drug candidate for a potent anti-cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy.Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [(18)F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day -1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed.Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day -1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses.Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased slightly by day 6. Our results indicate that single high-dose irradiation can produce a rapid, but reversible, vascular collapse in tumors. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate cerebral blood flow using arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging in patients with clinical seizure activity and determine its diagnostic performance in identifying seizure focus. Materials and Methods: Institutional Review Board of our hospital approved this retrospective study. Informed consent was waived. Clinical seizure focus was determined by a neurologist based on seizure semiology, electroencephalography, and conventional imaging modalities. The diagnostic performance of ASL perfusion MR imaging to identifying seizure focus compared to clinical seizure focus was analyzed. Results: Clinical seizure focus was localized in 95% (42/44) of patients. The sensitivity and specificity of ASL perfusion MR imaging for identifying seizure focus were 74% (95% CI: 58%, 86%) (clinical seizure focus was localizable in 31 of 42 patients, including complete concordance in 10 patients and partial concordance in 21 patients) and 0% (95% CI: 0%, 84%) (for the two patients whose clinical seizure foci were not localizable, they were identified by ASL perfusion MR imaging), respectively. Thus, the overall accuracy of ASL perfusion MR imaging for localizing seizure focus was 70% (33/44). For 4 patients who had abnormal perfusion on ASL, their seizure foci based on ASL perfusion MR imaging were discordant with clinical seizure foci. Conclusion: ASL perfusion MR imaging can provide information about perfusion status and important diagnostic clue in localizing seizure focus in patients with clinical seizure activity. It has the potential as a non-invasive complementary diagnostic tool for patients with clinical seizure activity. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the feasibility of 3D perfusion CT for predicting early treatment response in patients with liver metastasis from colorectal cancer. Methods: Seventeen patients with colon cancer and liver metastasis were prospectively enroled to undergo perfusion CT and 18F-FDG-PET/CT before and after one-cycle of chemotherapy. Two radiologists and three nuclear medicine physicians measured various perfusion CT and PET/CT parameters, respectively from the largest hepatic metastasis. Baseline values and reduction rates of the parameters were compared between responders and nonresponders. Spearman correlation test was used to correlate perfusion CT and PET/CT parameters, using RECIST criteria as reference standard. Results: Nine patients responded to treatment, eight patients were nonresponders. Baseline SUVmean30 on PET/CT, reduction rates of 30% metabolic volume and 30% lesion glycolysis (LG30) on PET/CT and blood flow (BF) and flow extraction product (FEP) on perfusion CT after chemotherapy were significantly different between responders and nonresponders (P =0.008–0.046). Reduction rates of BF (correlation coefficient=0.630) and FEP (correlation coefficient=0.578) significantly correlated with that of LG30 on PET/CT (P <0.05). Conclusion: CT perfusion parameters including BF and FEP may be used as early predictors of tumor response in patients with liver metastasis from colorectal cancer. [Copyright &y& Elsevier]

Abstract: Myocardial SPECT using 99mTc-sestamibi, 99mTc-tetrofosmin, 201Thallium is widely used in nuclear cardiology. Left ventricular systolic wall thickening (SWT) by SPECT and regional maximal elastance (rE max) using arterial tonometry were compared. rE max was calculated from time–pressure and time–volume curves. In normal heart, improvement of SWT was 4.1±11%, while 6.0±16% in dilated heart. Improvement of rE max was 0.67±1.0mmHg/mL in normal heart and 0.32±0.7mmHg/mL in dilated heart (p<0.05). rE max can be an alternative variable as an index of regional contractility. [Copyright &y& Elsevier]

Abstract: Although the clinical manifestations such as drowsiness, brisk reflexes, extensor plantar responses and hemisensory disturbance usually are considered to suggest Bickerstaff''s brainstem encephalitis (BBE) rather than Miller Fisher syndrome (MFS), the nosological relationship between BBE and MFS has yet to be established. Herein, we report upon a 58-year-old man who showed ophthalmoplegia, ataxia and consciousness disturbance. In the absence of any abnormality on brain MRI, electrophysiological studies and SPM analysis using 18F-FDG PET showed evidence of brainstem and cerebellum involvements. [Copyright &y& Elsevier]