Synthesis, Structure, and Optical Property of Tris(biaryldiyl)metal Complexes Consisting of Group 9 Elements.

We report the synthesis and characterization of tris(biphenyl-2,2'-diyl)metal complexes of trivalent group 9 elements (1M, M = Co, Rh, Ir) and their nonplanarly π-extended analogs, tris(1,1'-binaphthyl-2,2'-diyl)metal complexes (2M, M = Rh, Ir). Single crystal X-ray crystallography reveals the distorted octahedral geometry with an approximate C3 symmetry of trianionic complexes 1M (M = Co, Rh, Ir) and 2M (M = Rh, Ir), which are contacted by three Li+ ions in the crystal. Complex 1Ir exhibits yellow luminescence in THF with a photoluminescence quantum yield (ΦPL) of up to 0.73, along with a distinctive photophysical property, namely, a concentration dependence of the emission wavelength from 530 to 580 nm. This is a characteristic property of 1Ir and has not been observed in its isoelectronic analog, tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3). The concentration-dependent optical properties originate from the dissociation equilibria of Li+ ions from the anionic chromophore. Complex 2Ir also exhibits luminescence at 715 nm in THF, with a notable bathochromic shift from 1Ir through the π-extension. The findings offer insights into the photophysical properties of homoleptic organo-transition metal complexes, providing the foundation for the design of related transition metal complexes.

Synthesis, Structure, and Optical Property of [6]Cyclo-1,2-naphthylene.

A one-pot procedure with cobalt-mediated oxidation of 2,2'-dilithio-1,1'-binaphthyl by ferrocenium salts afforded the chiral cyclic hexamer of naphthylene, [6]cyclo-1,2-naphthylene (1). The molecular structure of 1 was determined by single crystal X-ray crystallography and NMR analyses, revealing its cyclic structure with an approximate D3 symmetry. Compound 1 exhibits blue emission at 383 nm with high photoluminescence quantum yield of 97 %, which can be attributed to its rigid twelve-membered ring structure. Optical resolution of 1 by chiral HPLC allowed for the evaluation of its chiroptical properties. Each enantiomer exhibits circular dichroism with complex Cotton effects, which are grouped into three positive or three negative couplets. Circularly polarized luminescence is observed at 383 nm with an anisotropy factor |glum| on the order of 10-4. The high photoluminescence quantum yield and the CPL properties of 1 indicate its potential application as a CPL emitter.

Computed tomography radiomic feature analysis of thymic epithelial tumors: Differentiation of thymic epithelial tumors from thymic cysts and prediction of histological subtypes.

PURPOSE: To investigate the value of computed tomography (CT) radiomic feature analysis for the differential diagnosis between thymic epithelial tumors (TETs) and thymic cysts, and prediction of histological subtypes of TETs. MATERIALS AND METHODS: Twenty-four patients with TETs (13 low-risk and 9 high-risk thymomas, and 2 thymic carcinomas) and 12 with thymic cysts were included in this study. For each lesion, the radiomic features of a volume of interest covering the lesion were extracted from non-contrast enhanced CT images. The Least Absolute Shrinkage and Selection Operator (Lasso) method was used for the feature selection. Predictive models for differentiating TETs from thymic cysts (model A), and high risk thymomas + thymic carcinomas from low risk thymomas (model B) were created from the selected features. The receiver operating characteristic curve was used to evaluate the effectiveness of radiomic feature analysis for differentiating among these tumors. RESULTS: In model A, the selected 5 radiomic features for the model A were NGLDM_Contrast, GLCM_Correlation, GLZLM_SZLGE, DISCRETIZED_HISTO_Entropy_log2, and DISCRETIZED_HUmin. In model B, sphericity was the only selected feature. The area under the curve, sensitivity, and specificity of radiomic feature analysis were 1 (95% confidence interval [CI]: 1-1), 100%, and 100%, respectively, for differentiating TETs from thymic cysts (model A), and 0.76 (95%CI: 0.53-0.99), 64%, and 100% respectively, for differentiating high-risk thymomas + thymic carcinomas from low-risk thymomas (model B). CONCLUSION: CT radiomic analysis could be utilized as a non-invasive imaging technique for differentiating TETs from thymic cysts, and high-risk thymomas + thymic carcinomas from low-risk thymomas.

Phase II study of S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Results of the LOGIK1605/JART-1501 study.

BACKGROUND: Combination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient. METHODS: Previously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m2 /day S-1 orally on days 1-14 plus 60 mg/m2 /day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy). RESULTS: Three patients were enrolled into the study. Toxicity and survival were assessable in all patients, but the treatment response was only assessable in one patient. The study was terminated because of poor case recruitment. The patients' characteristics were as follows: male/female = 2/1; PS 0/1 = 2/1; median age (range) = 59 (55-72); and stage III/IV = 2/1. The patient in which the treatment response was assessed exhibited SD (response rate: 0%). In both nonevaluable cases, the second course of chemotherapy was judged to be post-protocol treatment because it was delayed by ≥14 days, but a CR and PR were achieved after the end of the study, respectively. G4 leukopenia/neutropenia and G3 febrile neutropenia occurred in one patient each (33%). The median time to tumor progression was 17.6 months, and the 1-, 2-, 3-, and 4-year survival rates were 67, 33, 33, and 33%, respectively. The median overall survival time was not reached, and the 1-, 2-, 3-, and 4-year survival rates were 100, 67, 67, and 67%, respectively. CONCLUSIONS: Although it was difficult to recruit patients, there was a long-term survivor >4 years who appeared to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma.

Imaging findings of lesions in the middle and posterior mediastinum.

Lesions in the middle and posterior mediastinum are relatively rare, but there are some useful radiological clues that can be used to diagnose them precisely. It is useful to determine the affected mediastinal compartment and the locations of the main thoracic nerves on medical images for diagnosing such mediastinal lesions. Neurogenic tumors can occur in the middle mediastinum, although they generally arise as posterior mediastinal tumors. Based on the above considerations, we review various characteristic imaging findings of middle and posterior mediastinal lesions, and their differential diagnoses.

A simple and reliable method to preoperatively detect a common trunk of the left pulmonary vein.

BACKGROUND: It is difficult to detect a common trunk of the left pulmonary vein (PV) preoperatively, which may cause intraoperative accidental complications. The purpose of this study is to establish a simple and reliable method of detecting a common trunk in preoperative computed tomography (CT) images. METHODS: A total of 428 patients who underwent thin-section CT preoperatively for left lung cancer at 4 institutions were reviewed. The characteristic findings of a common trunk in the axial view were considered by confirming the preoperative CT findings of cases that had been verified to have a common trunk based on intraoperative findings. The CT images were reviewed independently by two evaluators. RESULTS: We found that the distance between the mediastinal side of the left lower bronchus and the junction of two left PVs was extremely short in the cases with a common trunk in the axial view. In a typical case, the axial section of the bronchus is close to the junction. Of the 416 patients that were evaluable among the 428 total patients, 26 (6.3%) were diagnosed as having a common trunk by both evaluators, and the diagnosis was coincident in 413 patients (99.2%). We were able to evaluate the surgical videos of 16 of the 26 patients, and a common trunk was confirmed in 15 patients (94%). CONCLUSIONS: We established a simple and reliable method of detecting a common trunk of the left PV in the axial view on chest CT that was routinely performed prior to lung cancer surgery.

S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Study protocol of LOGIK1605/JART-1501.

Thymic carcinoma is a rare epithelial tumor of the thymus with a poor prognosis, and multimodal approaches are important for its treatment. Recently, a number of studies have indicated that S-1 treatment is effective against thymic carcinoma. S-1 plus cisplatin with concurrent radiotherapy is a commonly used treatment for other malignancies, including non-small cell lung cancer (NSCLC). In addition, its safety has been confirmed, and it has been reported to have a marked effect against thymic carcinoma. Therefore, we conducted a phase II study of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced thymic carcinoma, in which the overall response rate was employed as the primary endpoint. The secondary endpoints were overall survival, progression-free survival, and safety.

Visibility of the hilar lymph nodes using advanced virtual monoenergetic low-keV images for preoperative evaluation of lung cancer.

OBJECTIVE: The purpose of our study was to evaluate the visibility of the hilar lymph nodes (LNs) using advanced virtual monoenergetic low-keV images compared with early-phase contrast-enhanced CT. METHODS: Dual energy contrast-enhanced CT was performed for pre-operative evaluation of lung cancer at 20 and 60 s after administration of contrast media in 50 patients (32 males and 18 females; mean age, 69 years). Five kinds of images (A: 20 s/120 kV; B: 60 s/40 keV; C: 60 s/50 keV; D: 60 s/120 kV; E: 60 s/100 kV) were reconstructed. We measured the CT number of the bilateral main pulmonary arteries (PAs), pulmonary veins (PVs) and hilar LNs, and evaluated the differences in CT number (Hounsfield units, HUs) between the PA/PV and LNs (PA-LN and PV-LN contrast). Artifacts from the superior vena cava (SVC) were also evaluated. RESULTS: The mean PA-LN contrast (HU) was 415 in image group A, 299 in B, 180 in C, 80 in D, and 100 in E. The mean PV-LN contrasts in each group were 306, 287, 177, 78, and 99, respectively. Image group B showed the second highest PA-LN contrast following image group A. There was no significant difference in the PV-LN contrast between image groups A and B. The PA-LN and PV-LN contrasts of image groups B and C were significantly higher than those of E. SVC artifacts were lower in the delayed-phase images (Group B-E) than in Group A. CONCLUSION: To evaluate the hilar LNs with a single image series, advanced virtual monoenergetic 40-keV imaging at the delayed 60-s phase seems to be the most valuable. ADVANCES IN KNOWLEDGE: Advanced virtual monoenergetic image is useful for evaluation of both hilar LNs and tumors in the delayed phase without artifact derived from the streak artifact from dense contrast media in the SVC.

Transient increases in serum α fetoprotein and protein induced by vitamin K antagonist II levels following proton therapy does not necessarily indicate progression of hepatocellular carcinoma.

Transient increases in α-fetoprotein (AFP) and protein induced by vitamin K antagonist II (PIVKA-II), so-called flares, are frequently observed after treatment of hepatocellular carcinoma (HCC). In the present study, changes in AFP and PIVKA-II levels after proton therapy (PT), and the relationship between the flare phenomenon and clinical response were investigated. In 82 patients with stage I/II HCC (59 with no recurrence and 23 with out-of-field recurrence within 1 year), serum AFP and PIVKA-II levels were measured at 1, 3, 6, 9 and 12 months post-PT. AFP and PIVKA-II flares were defined as a >20% increase from the preceding serum level above 20 ng/ml (AFP) or 40 mAU/ml (PIVKA-II), followed by a >20% drop. Among the 59 patients with no recurrence, 3 (5.1%) had an AFP flare, while 23 (39%) had a PIVKA-II flare. The median time to AFP and PIVKA-II flare peaks was 1 and 6 months, respectively. In 4 patients, PIVKA-II flares were observed twice during follow-up. In 1 patient, AFP and PIVKA-II flares were observed simultaneously at 1 month post-PT. The PIVKA-II level pre-PT was significantly higher in the PIVKA-II flare-positive group compared with that in the flare-negative group (P=0.015, odds ratio 4.3, 95% confidence interval, 1.3-14.0). In the 23 patients with out-of-field recurrence, the median increase rate of PIVKA-II (203%) was higher than that in the PIVKA-II-flare-positive group (111%, P=0.035) and the time to recurrence (median, 9 months) was longer than the time to peak AFP level (1 month) in the AFP-flare-positive group (P=0.033). There was no significant association between flares and clinical response. Increases in AFP and PIVKA-II levels following PT should be assessed with caution to avoid misinterpretation of therapeutic outcome.

Hematuria Alone or in Combination with Proteinuria Is a Harbinger of Poor Prognosis in Patients with Non-Hodgkin Lymphoma.

BACKGROUND: Screening for hematuria is essential during health checkups in the general population. However, urine examinations in patients with cancer tend to be overlooked. This study attempted to demonstrate the novel utility of urinalysis in the assessment of the prognosis of non-Hodgkin lymphoma (NHL). METHODS: A longitudinal, retrospective cohort study was conducted to examine the association between hematuria and mortality in 294 patients with NHL. Urinalysis was performed using a dipstick test. A multivariate, logistic regression model was constructed to evaluate factors associated with the presence of hematuria. Statistical association between hematuria and the time to all-cause mortality was analyzed using Kaplan-Meier analysis, followed by multivariate proportional hazards regression analysis adjusted for covariates that might be related to mortality. RESULTS: The prevalence of hematuria alone and in combination with proteinuria was 11.6 and 5.1%, respectively. C-reactive protein was a significant factor associated with the presence of hematuria (OR [95% CI] 1.17 [1.03-1.34], p = 0.0194). The cumulative mortality was significantly higher in patients with hematuria alone (51.1%), proteinuria alone (47.1%), and both (66.7%), than in those with neither (24.3%). Moreover, the presence of hematuria alone was significantly associated with all-cause mortality (hazard ratio [95% CI] 1.78 [1.10-3.50], p = 0.0455), and patients with concomitant proteinuria were at the highest risk (4.01 [1.71-8.33], p = 0.0001). CONCLUSIONS: In patients with hematuric NHL, systemic inflammation is likely to develop to such a great extent that kidney damage occurs. Therefore, the presence of hematuria, alone or especially in combination with proteinuria, predicts a poor prognosis of NHL.

Hepcidin-25/erythroferrone ratio predicts improvement of anaemia in haemodialysis patients treated with ferric citrate hydrate.

BACKGROUND/AIMS: Hepcidin-25 (HEP-25) and erythroferrone (ERFE) are key regulators of iron homeostasis. Correlations among serum ferritin, ERFE and HEP-25 levels and improvements in anaemia have not been evaluated after administration of ferric citrate hydrate (FCH). METHODS: This retrospective observational study investigated 24 patients on haemodialysis with both anaemia (haemoglobin (Hb) < 12 g/dL) and hyperphosphatemia (inorganic phosphorus ≥6 mg/dL). The patients who were administered FCH (1500 mg/day) for 12 consecutive weeks and 12 control patients who were administered a phosphate binder other than FCH were included. Correlations among Hb, HEP-25 and ERFE levels were studied. We then stratified the FCH group into two subgroups using the median baseline values of ferritin, HEP-25, ERFE and HEP-25/ERFE ratio to predict whether these markers could serve as prognostic indicators in the treatment of anaemia. RESULTS: In the FCH group, Hb, transferrin saturation, ferritin, HEP-25 and ERFE levels were all significantly increased, while inorganic phosphorus levels, dosage of erythropoietin-stimulating agent, and erythropoietin resistance index were all significantly decreased after drug administration. A significant inverse correlation was apparent between Hb and HEP-25 levels, and a significant positive correlation was seen between Hb and ERFE levels. A significant inverse correlation was found between HEP-25 and serum ERFE levels. Compared with the high HEP-25/ERFE ratio group, only the low HEP-25/ERFE ratio group exhibited significantly increased Hb levels at 12 weeks. CONCLUSION: HEP-25/ERFE ratio could be a novel prognostic marker for increases in Hb levels following FCH administration.

Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl-xL pathway.

Vasoactive intestinal peptide (VIP) is a modulator of inflammatory responses. VIP receptors are expressed in several tumor types, such as colorectal carcinoma. The study described herein was conducted to confirm the presence of VIP and its receptors (VPAC1 and VPAC2) in surgically resected hepatocellular carcinoma (HCC) tissues and in the HCC cell line Huh7. The mechanism responsible for apoptosis of HCC cells was then examined because VIP treatment (10-10  M) significantly suppressed proliferation of Huh7 cells. In examining apoptosis-related proteins, we found caspase-3 to be significantly increased and Bcl-xL and cyclic AMP (cAMP) response element-binding protein (CREB) to be significantly decreased in Huh7 cells cultured with VIP. Furthermore, the CREB level and phosphorylation were reduced. These effects were reversed by the addition of VIP receptor antagonist or cAMP antagonist Rp-cAMPS. Pretreatment with cAMP analogue blocked the increased apoptosis, suggesting that VIP induces apoptosis via a PKA-independent signaling mechanism. Our data indicate that VIP prevents the progression of HCC by apoptosis through the cAMP/Bcl-xL pathway.

Anticentromere Antibody-positive Scleroderma Renal Crisis Requiring Dialysis.

A 70-year-old man with prior Raynaud's phenomena developed hypertension and renal insufficiency. Raynaud's phenomena, finger skin thickening, interstitial lung disease, and positive anticentromere antibody findings indicated systemic sclerosis (SSc). Based on the presence of SSc, severe hypertension with rapidly progressive renal failure, and proliferative and obliterative arteriolar vasculopathy, scleroderma renal crisis (SRC) was diagnosed. Despite good blood pressure control with antihypertensive drugs, hemodialysis was initiated and could not be withdrawn owing to unimproved renal dysfunction. Although SRC in anticentromere antibody-positive limited cutaneous SSc is extremely rare, some patients may develop SRC, and their renal prognosis may be poor.

Useful computed tomography features for differentiating between focal atelectasis and pleural dissemination on preoperative evaluations of thymic epithelial tumors.

PURPOSE: Distinguishing between focal atelectasis (FA) and pleural dissemination (PD) is important for determining the optimal therapeutic strategy for thymic epithelial tumors (TET). This study aimed to identify useful computed tomography (CT) features for distinguishing between these two conditions. MATERIALS AND METHODS: We retrospectively analyzed preoperative CT images of 27 TET, which included 40 PD and 40 FA lesions. Two radiologists independently interpreted the pleural lesions without knowing the final diagnosis. The CT images were evaluated to assess the lesion location, size, and shape, presence of a spinous shadow and ground glass opacities (GGO) near to the lesion, and the shortest distance from the lesion to the nearest peripheral pulmonary artery (PA). RESULTS: FA lesions tended to occur on the dorsal side (90%, P = 0.024); have shorter major and minor axes (P < 0.001), a triangular shape (43%, P = 0.002), a spinous shadow (45%, P = 0.001) and GGO (28%, P = 0.006); and be close to a peripheral PA (P = 0.007). Ninety percent of PD lesions were located in the left thorax, and all of them were ipsilateral to the tumor (both P < 0.001). The 9 examined factors exhibited sensitivity, specificity, positive predictive, and negative predictive values of 85%, 95%, 94%, and 86%, respectively, for diagnosing FA (when ≥3 factors were present), and 90%, 48%, 63%, and 83%, respectively, for diagnosing PD (when ≥4 factors were present). CONCLUSION: The site, size, and shape of a lesion; the presence of a spinous shadow/GGO; and the distance to the nearest PA are useful for distinguishing between PD and FA.

Prevalence and mortality of chronic kidney disease in lymphoma patients: A large retrospective cohort study.

In patients with lymphoma, an important issue that has been recognized is renal involvement, including glomerulonephritis, acute kidney injury, and lymphoma infiltrating the kidney. However, the prevalence and mortality of chronic kidney disease (CKD) have not been fully understood in lymphoma patients. This study aimed to evaluate the prevalence of CKD and its impact on mortality in those patients.This was a retrospective cohort study of 429 consecutive lymphoma patients who were admitted or regularly visited our hospital from January 2013 to October 2016. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m and/or proteinuria ≥ 1+ that was sustained for at least 3 months. The prevalence of CKD at enrollment was evaluated according to the modified CKD classification by Kidney Disease: Improving Global Outcomes (KDIGO) (eGFR and proteinuria category). Dipstick proteinuria was classified into 3 grades: A1 for - and ±; A2 for 1+ or 2+; and A3 for ≥3+. The eGFR (mL/min/1.73 m) was classified into 6 stages: G1 for ≥90, G2 for 60 to 89, G3a for 45 to 59, G3b for 30 to 44, G4 for 15 to 29, and G5 for <15. The cumulative mortality rate was estimated using the Kaplan-Meier method, with stratification into 2 groups based on the presence or absence of CKD. Furthermore, a multivariate Cox proportional hazards regression model was used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for all-cause mortality, after adjustments for age, sex, pathologic type, clinical stage of lymphoma, presence or absence of diabetes mellitus, hypertension, and cardiovascular disease.The mean follow-up period was 3.06 ±â€Š0.96 years, and the prevalence of CKD at study enrollment was 34.5%. The cumulative mortality rate was 20.7%, and was significantly higher in the CKD group than in the group without CKD (36.4% vs 18.0%, P = .02). Multivariate analysis found mortality to be significantly associated with CKD (HR 1.58; 95% CI, 1.01-2.46), and this association was the most robust with very high-risk CKD (HR 6.94; 95% CI, 2.50-17.33).The prevalence of CKD in lymphoma patients was high. CKD should be considered an independent risk factor for mortality among patients with lymphoma.

Identification of the pericardiacophrenic vein on CT.

BACKGROUND: To evaluate the depictability of pericardiacophrenic veins (PCPV) as landmarks for the location of the phrenic nerves on multi-detector-row computed tomography (MDCT), and to investigate the usefulness of depicting the PCPV to aid differential diagnosis of anterior mediastinal lesions. METHODS: Fifty-six patients with anterior mediastinal lesions (Fifty lesions originated from the thymus, six were of non-thymic origin) were evaluated. Contrast-enhanced CT scans of the chest were performed in all cases before diagnosis, and 22 of these scans were performed with electrocardiographic (ECG) gating. Two chest radiologists assessed the depictability of the PCPV and the positional relationship between the center of each anterior mediastinal lesion and the ipsilateral PCPV. RESULTS: The use of ECG gating increased the PCPV depiction rate in the lower left part of the mediastinum. The depiction rate of the left PCPV was significantly higher than that of the right PCPV. All 50 tumors of thymic origin and 3 of the 6 tumors of non-thymic origin were located on the medial side of the ipsilateral PCPV. The 3 lesions located on the lateral side of the ipsilateral PCPV were of non-thymic origin (p = 0.0007). CONCLUSION: The use of ECG gating during MDCT may improve the depictability of the PCPV in the lower left section of the anterior mediastinum. Solitary anterior mediastinal lesions located on the lateral side of the ipsilateral PCPV are likely to be of non-thymic origin.

New technique of percutaneous CT fluoroscopy-guided marking before video-assisted thoracoscopic surgery for small lung lesions: feasibility of using a 25-gauge needle without local anaesthesia.

OBJECTIVE: To retrospectively evaluate the feasibility of CT fluoroscopy-guided percutaneous marking using a 25-gauge needle and indigo carmine before video-assisted thoracoscopic surgery (VATS) for small lung lesions. METHODS: 21 patients, 14 males and 7 females, with a median age of 69 years (range, 40-79), underwent CT fluoroscopy-guided percutaneous VATS marking using a 25-gauge, 70-mm needle and 1.5-ml indigo carmine. The mean diameter of the lung lesions was 14 mm (range, 6-27). We evaluated the technical success rate, surgical success rate and complications related to this procedure by reviewing medical records and images. Technical success was defined as completion of this procedure. Surgical success was defined as resection of the target lesion with negative margins on pathological examination after VATS. Complications that required advanced levels of care were classified as major complications, and the remaining complications were considered minor. RESULTS: The technical success rate was 100%. In all cases, VATS was successfully performed as planned, and the target lesion was resected with negative margins on pathological examination after VATS. Thus, the surgical success rate was 100%. Mild pneumothorax was found in two cases, but further treatment was not required. The minor complication rate was 9.5% (2/21), and major complication rate was 0%. Only two patients (9.5%) complained of slight pain upon puncture, but local anaesthesia was not required. CONCLUSION: Percutaneous CT fluoroscopy-guided VATS marking using a 25-gauge needle without local anaesthesia appears feasible and safe. Advances in knowledge: This technique expands a possibility of the CT-guided marking.