HER2-low gastric cancer: is the subgroup targetable?

Therapeutic developments in the targeting of human epidermal growth factor receptor 2 (HER2)-expressing gastric cancer have followed the dramatic success of HER2-expressing breast cancer treatment, which has facilitated the expansion of indications for anti-HER2 agents to include not only conventional HER2-positive breast cancer, but also HER2-low and HER2-ultralow subgroups. The targetability of HER2-low gastric cancer, however, has yet to be established. Hence, further studies are needed to comprehensively understand the clinicopathological features, specific gene alterations, and distinct tumor immune microenvironment of HER2-low gastric cancer and compare them with those for HER2-positive or -negative gastric cancer. Antibody-drug conjugates for HER2 play an important role in making HER2-low gastric cancer targetable. In this context, a deeper understanding of the novel anti-HER2 agents, including antibody-drug conjugates, bispecific T-cell engager antibodies, and a combination of these agents, as well as new forms of immunomodulatory agents are also required. Redefining and re-categorizing HER2 status through not only immunohistochemistry/fluorescence in situ hybridization but also evaluating ERRB2 copy number gain or protein overexpression levels measured using DNA or RNA sequencing might be helpful for identifying populations with HER2-expressing tumors who would ideally benefit from anti-HER2 treatment. The current paper reviewed recent clinical trials, focusing particularly on HER2-low gastric cancer together with basic/translational findings, and discuss perspectives on further therapeutic development in the treatment of this distinct subgroup.

Inguinal hernia repair in patients with artificial urinary sphincter after radical prostatectomy.

PURPOSE: Stress urinary incontinence (UI) often develops after radical prostatectomy for prostate cancer, and in those patients with moderate-to-severe stress UI an artificial urinary sphincter (AUS) is implanted. Inguinal hernias (IHs) often occur after radical prostatectomy. As the prevalence of AUS implantation increases, it is possible to encounter patients with IHs undergoing AUS implantation (IHA). This study investigated our treatment and discussed an appropriate approach for IHAs. METHODS: We retrospectively investigated patients who underwent IH repair with AUS implantation at our hospital from January 2018 to March 2023. We classified IHAs into Types A-D based on the positions of the IHs and AUS devices (the positions of the control pump, pressure-regulating balloon, and connecting tube). The hernia and control pump were ipsilateral in Types A and B, whereas the hernia and pressure-regulating balloon were ipsilateral in Types A and C. RESULTS: This study included 12 IHs of 11 patients. The median patient age was 77 years. We conducted open repair in nine patients with all types and laparoscopic repair in two patients with Type B. The median operation times for unilateral and bilateral repairs were 96 and 182 min, respectively. There were no complications with AUS or hernia surgeries. CONCLUSION: IHA has its own characteristics, and multidisciplinary knowledge thereof will help surgeons safely perform IH surgery.

Incidence, clinicopathological features, and clinical outcomes of low HER2 expressed, inoperable, advanced, or recurrent gastric/gastroesophageal junction adenocarcinoma.

BACKGROUND: According to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma. PATIENTS AND METHODS: This was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-), and HER2-positive (IHC2+/ISH+ or 3+). RESULTS: In total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n = 410; HER2-low, n = 154, and HER2-positive, n = 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.59-0.89; P = 0.002]. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR = 1.01, 95% CI 0.82-1.23; P = 0.843). CONCLUSIONS: Patients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group's prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required.

Correlation between magnesium pre-loading and cisplatin-induced nephrotoxicity in 5-fluorouracil/cisplatin combination therapy for esophageal cancer.

The use of cisplatin may cause nephrotoxicity in patients. Hydration solutions supplemented with magnesium could reduce cisplatin-induced nephrotoxicity. In this study, we evaluated the preventive effect of magnesium pre-loading on cisplatin-induced nephrotoxicity in patients with esophageal cancer. We retrospectively evaluated the prevalence of, and risk factors for, nephrotoxicity in 160 patients with esophageal cancer treated with the 5-fluorouracil/cisplatin regimen from 2014 to 2016 with and without magnesium supplementation. Significant differences were observed between the magnesium and non-magnesium groups in terms of frequency of estimated creatinine clearance of grade 2 or higher that was at 4% (n = 3) and 13% (n = 10) (p = 0.027), respectively. The logistic regression analysis revealed that eCcr of grade 2 or higher was significantly associated with the non-magnesium regimen (odds ratio (OR), 4.175; 95% confidence interval (CI) = 1.061-16.430; p = 0.041) and age ≥ 65 years (OR, 13.951; 95% CI = 1.723-112.974; p = 0.014). This study suggests that 20 mEq magnesium pre-loading significantly reduces the prevalence of cisplatin-induced nephrotoxicity. Furthermore, when cisplatin is administered to individuals older than 64 years, a close observation for the onset of cisplatin-induced nephrotoxicity is crucial.

Effects of Oral Management on Elderly Patients with Pneumonia.

OBJECTIVES: In this study, we examined the factors influencing the presence or absence of dental intervention in patients with pneumonia in an acute-care hospital, focusing on oral intake and its status. DESIGN: Observational study. SETTING: Teikyo University School of Medicine, Mizonokuchi Hospital. PARTICIPANTS: Patients ≥65 years of age who were admitted to the Teikyo University School of Medicine, Mizonokuchi Hospital between January 1, 2018 and December 31, 2019 with pneumonia who were referred to the Department of Rehabilitation with suspected dysphagia were included in the study. Fifty patients who underwent dental intervention were compared with 50 controls who had received no dental interventions prior to the opening of the dental department. MEASUREMENTS: Time series matching was retrospectively performed using the Oral Health Assessment Tool (OHAT). From the medical records, age at admission, sex, pneumonia severity classification (age, dehydration, respiratory failure, orientation disturbance, and blood pressure [A-DROP] score), body mass index, Charlson's Comorbidity Index, OHAT, functional oral intake scale (FOIS) score at admission and discharge, and the length of hospital stay were retrieved; FOIS level ≥4 was defined as established oral intake. RESULTS: The number of patients in the control group before matching was 179. Twelve patients with missing information and seven patients who died in the hospital were excluded from this study. Multivariable logistic regression analysis showed that dental intervention (odds ratio 3.0, p = 0.014) was associated with the establishment of oral intake at discharge. Multiple logistic regression analysis showed that dental intervention was a significant factor for FOIS at discharge (p = 0.002) and the length of hospital stay (p = 0.039). CONCLUSION: Oral management with dental intervention was associated with establishing oral intake and reducing hospital stay in patients with pneumonia, regardless of pneumonia severity or comorbidities.

A novel clinical prognostic index for patients with advanced gastric cancer: possible contribution to the continuum of care.

BACKGROUND: The Japan Clinical Oncology Group (JCOG) prognostic index, consisting of performance status, primary tumor resected, number of metastases, and serum alkaline phosphatase, has been one of the robust prognostic indices for patients with advanced gastric cancer on the basis of which clinical trials have stratified prognosis. Only a few studies, however, have utilized the JCOG prognostic index in daily practice. METHODS: We conducted a retrospective study on patients with advanced gastric cancer who received first-line platinum-containing chemotherapy at a single institute between 2011 and 2017. Prognostic factors were evaluated using a Cox proportional regression model. RESULTS: A total of 608 patients were enrolled. Multivariate analysis showed that performance status ≥1, presence or absence of primary tumor, serum alkaline phosphatase, neutrophil-to-lymphocyte ratio ≥4, and diffuse-type histology were significantly associated with worse prognosis, whereas the number of metastases was not. Although the original prognostic index could not adequately stratify patients into three risk groups, the modified index (good: 0 and 1, moderate: 2 and 3, poor: 4-6), which was established by incorporating diffuse-type histology and high neutrophil-to-lymphocyte ratio, demonstrated excellent stratification. The median overall survival of the good (n = 315), moderate (n = 243), and poor (n = 54) risk groups was 20.5, 13.5, and 10.2 months, respectively. Hazard ratios (HRs) were 1.69 [95% confidence interval (CI), 1.40-2.04; good versus moderate] and 1.52 (95% CI, 1.11-2.08; moderate versus poor). This novel index also demonstrated a statistically significant stratification of survival after progression following first-line chemotherapy (good versus moderate: HR, 1.41; 95% CI, 1.16-1.70; moderate versus poor: HR, 2.00; 95% CI, 1.45-2.74). CONCLUSIONS: The modified JCOG prognostic index showed excellent stratification of overall survival in real-world patients, which could also help determine the need for treatment changes throughout the continuum of chemotherapy.

Impact of the 12-gene recurrence score assay on deciding adjuvant chemotherapy for stage II and IIIA/B colon cancer: the SUNRISE-DI study.

BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.

Electronic and spin structures of CaMn4Ox clusters in the S0 state of the oxygen evolving complex of photosystem II. Domain-based local pair natural orbital (DLPNO) coupled-cluster (CC) calculations using optimized geometries and natural orbitals (UNO) by hybrid density functional theory (HDFT) calculations.

Domain-based local pair natural orbital (DLPNO) coupled cluster single and double (CCSD) with triple perturbation (T) correction methods were performed to elucidate the relative stabilities of ten different intermediate structures of the CaMn4Ox cluster in the S0 state of the oxygen evolving complex (OEC) of photosystem II (PSII). Full geometry optimizations of all the S0 intermediates were performed by the UB3LYP-D3/Def2-TZVP methods, providing the assumed geometrical structures and starting natural orbitals (UNO) for DLPNO-CCSD(T)/Def2TZVP calculations. The effective exchange integrals (J) for the spin Hamiltonian models for the ten intermediates were obtained by the UB3LYP/Def2-TZVP calculations followed by the general spin projections. DLPNO-CCSD(T) calculations followed by the CBS extrapolation procedure elucidated that the (II, III, IV, IV) and (III, III, III, IV) valence states in the CaMn4O5 cluster of the OEC of the PS II were nearly degenerated in energy in the S0 state, indicating an important role of dynamical electron correlation effects for the valence and spin fluctuations in strongly correlated electron systems (SCESs) consisting of 3d transition metals.

Assessment of transporter-mediated efflux of nintedanib using in vitro cell line models of idiopathic pulmonary fibrosis.

Objective: We aimed to investigate the involvement of efflux transporters, including multidrug resistant protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), MRP2, and breast cancer resistance protein (BCRP), in the intracellular accumulation of the antifibrotic agent nintedanib in fibrotic lung cells. Methods: We used transforming growth factor-ß1 (TGF-ß1)-treated human lung fibroblasts (WI-38) and alveolar epithelial cells (A549) as in vitro models. The expression and activities of efflux transporters in TGF-ß1-treated WI-38 and A549 cells were evaluated using immunoblotting and flow cytometry. Cells were treated with nintedanib and then incubated with inhibitors of these transporters. The intracellular concentration of nintedanib was determined. Results: MDR1, MRP1, MRP2, and BCRP were found to be expressed in WI-38 and A549 cells with or without TGF-ß1 stimulation, with the exception of MRP2 in WI-38 cells. The efflux activities of these transporters were observed in these cells. MDR1 inhibitors significantly increased the intracellular accumulation of nintedanib, whereas MRP inhibitors did not show an effect. The BCRP inhibitor significantly increased the transporter activity in A549 cells but not in WI-38 cells. Conclusion: This study suggests that the efflux via MDR1 and BCRP is involved in the intracellular accumulation of nintedanib in fibrotic lung cells.

Neutropenia and survival outcomes in metastatic colorectal cancer patients treated with trifluridine/tipiracil in the RECOURSE and J003 trials.

BACKGROUND: The phase II J003 (N = 169) and phase III RECOURSE (N = 800) trials demonstrated a significant improvement in survival with trifluridine (FTD)/tipiracil (TPI) versus placebo in patients with refractory metastatic colorectal cancer. This post hoc analysis investigated pharmacokinetic data of FTD/TPI exposure and pharmacodynamic markers, such as chemotherapy-induced neutropenia (CIN) and clinical outcomes. PATIENTS AND METHODS: A total of 210 patients from RECOURSE were enrolled in this substudy. A limited sampling approach was used, with three pharmacokinetic samples drawn on day 12 of cycle 1. Patients were categorized as being above or below the median area under the plasma concentration-time curve (AUC) for FTD and TPI. We conducted a post hoc analysis using the entire RECOURSE population to determine the correlations between CIN and clinical outcome. We then carried out a similar analysis on the J003 trial to validate the results. RESULTS: In the RECOURSE subset, patients in the high FTD AUC group had a significantly increased CIN risk. Analyses of the entire population demonstrated that FTD/TPI-treated patients with CIN of any grade in cycles 1 and 2 had significantly longer median overall survival (OS) and progression-free survival (PFS) than patients who did not develop CIN and patients in the placebo group. Patients who required an FTD/TPI treatment delay had increased OS and PFS versus those in the placebo group and those who did not develop CIN. Similar results were obtained in the J003 cohort. CONCLUSIONS: In RECOURSE, patients with higher FTD drug exposure had an increased CIN risk. FTD/TPI-treated patients who developed CIN had improved OS and PFS versus those in the placebo group and those who did not develop CIN. Similar findings were reported in the J003 cohort, thus validating the RECOURSE results. The occurrence of CIN may be a useful predictor of treatment outcomes for FTD/TPI-treated patients. CLINICALTRIALS. GOV IDENTIFIER: NCT01607957 (RECOURSE). JAPAN PHARMACEUTICAL INFORMATION CENTER NUMBER: JapicCTI-090880 (J003).

Factors associated with masseter muscle quality assessed from ultrasonography in community-dwelling elderly individuals: A cross-sectional study.

BACKGROUND: Associations between masseter muscle thickness(MMT) and limb muscle thickness, and between grip strength and MMT, as well as tooth-loss, have been reported previously. The previous study also showed that masseter muscle mass could be a better marker of sarcopenia than psoas muscle mass. Although the association between MMT and muscle strength is also known, the quality of the masseter muscle were not assessed in detail previously. We examined the relationship of masseter muscle echo intensity (MMEI) with skeletal muscle, physical function, and nutrition status, in order to determine whether MMEI could be a good indicator of these parameters. METHODS: We assessed 139 community-dwelling elderly individuals (men: 65, women: 74). Age, body mass index (BMI), skeletal muscle mass index, grip strength, walking speed, calf circumference, tooth-loss (Eichner classification), occlusal force, MMT, and MMEI were obtained. In multiple regression analysis, MMEI were set as dependent variables. RESULTS: Multiple regression analysis revealed BMI (p < 0.05), grip strength (p < 0.01), walking speed (p < 0.01), and MMT (p < 0.01) as factors with significant association with MMEI. CONCLUSIONS: MMT is related to occlusal force and MMEI. MMEI was related strongly to grip strength and walking speed, but not to tooth-loss. However, MMEI, which is easily determined ultrasonographically, could be a good indicator of grip strength and walking speed, and thus may be predictive of dynapenia.

Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase III study.

Background: : Second-line treatment with ramucirumab+FOLFIRI improved overall survival (OS) versus placebo+FOLFIRI for patients with metastatic colorectal carcinoma (CRC) [hazard ratio (HR)=0.84, 95% CI 0.73-0.98, P = 0.022]. Post hoc analyses of RAISE patient data examined the association of RAS/RAF mutation status and the anatomical location of the primary CRC tumour (left versus right) with efficacy parameters. Patients and methods: Patient tumour tissue was classified as BRAF mutant, KRAS/NRAS (RAS) mutant, or RAS/BRAF wild-type. Left-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum; right-CRC included transverse, ascending colon, and cecum. Results: RAS/RAF mutation status was available for 85% of patients (912/1072) and primary tumour location was known for 94.4% of patients (1012/1072). A favourable and comparable ramucirumab treatment effect was observed for patients with RAS mutations (OS HR = 0.86, 95% CI 0.71-1.04) and patients with RAS/BRAF wild-type tumours (OS HR = 0.86, 95% CI 0.64-1.14). Among the 41 patients with BRAF-mutated tumours, the ramucirumab benefit was more notable (OS HR = 0.54, 95% CI 0.25-1.13), although, as with the other genetic sub-group analyses, differences were not statistically significant. Progression-free survival (PFS) data followed the same trend. Treatment-by-mutation status interaction tests (OS P = 0.523, PFS P = 0.655) indicated that the ramucirumab benefit was not statistically different among the mutation sub-groups, although the small sample size of the BRAF group limited the analysis. Addition of ramucirumab to FOLFIRI improved left-CRC median OS by 2.5 month over placebo (HR = 0.81, 95% CI 0.68-0.97); median OS for ramucirumab-treated patients with right-CRC was 1.1 month over placebo (HR = 0.97, 95% CI 0.75-1.26). The treatment-by-sub-group interaction was not statistically significant for tumour sidedness (P = 0.276). Conclusions: In the RAISE study, the addition of ramucirumab to FOLFIRI improved patient outcomes, regardless of RAS/RAF mutation status, and tumour sidedness. Ramucirumab treatment provided a numerically substantial benefit in BRAF-mutated tumours, although the P-values were not statistically significant. ClinicalTrials.gov number: NCT01183780.

Caste-specific microRNA expression in termites: insights into soldier differentiation.

Eusocial insects have polyphenic caste systems in which each caste exhibits characteristic morphology and behaviour. In insects, caste systems arose independently in different lineages, such as Isoptera and Hymenoptera. Although partial molecular mechanisms for the development of eusociality in termites have been clarified by the functional analysis of genes and hormones, the contribution of microRNAs (miRNAs) to caste differentiation is unknown. To understand the role of miRNAs in termite caste polyphenism, we performed small RNA sequencing in a subterranean termite (Reticulitermes speratus) and identified the miRNAs that were specifically expressed in the soldier and worker castes. Of the 550 miRNAs annotated in the R. speratus genome, 74 were conserved in insects and 174 were conserved in other termite species. We found that eight miRNAs (mir-1, mir-125, mir-133, mir-2765, mir-87a and three termite-specific miRNAs) are differentially expressed (DE) in soldiers and workers of R. speratus. This differential expression was experimentally verified for five miRNAs by real-time quantitative PCR. Further, four of the eight DE miRNAs in soldier and worker termite castes were also differentially expressed in hymenopteran castes. The finding that Isoptera and Hymenoptera shared several DE miRNAs amongst castes suggests that these miRNAs evolved independently in these phylogenetically distinct lineages.

Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4).

BACKGROUND: Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. PATIENTS AND METHODS: Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. RESULTS: Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. CONCLUSION: Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. CLINICALTRIALS.GOV ID: NCT02746796.

External validation of ADNEX MR SCORING system: a single-centre retrospective study.

AIM: To evaluate the accuracy of the ADNEX MR SCORING system for characterising adnexal masses. MATERIALS AND METHODS: An institutional review board approved this retrospective study. The study population comprised 663 women who underwent magnetic resonance imaging (MRI) from January 2007 to December 2014 to characterise 778 adnexal masses that were indeterminate under ultrasonography (590 benign and 188 malignant). Two radiologists independently reviewed the MRI images. The masses were scored from 1 to 5 according to the ADNEX MR SCORING system. The diagnostic performance of the system was evaluated by receiver operating characteristic (ROC) analysis. Masses scored 4 or greater were considered malignant (including tumours of borderline malignancy or low malignant potential). RESULTS: The malignancy rates of masses with scores of 2, 3, 4 and 5 were 1.9% (8/419), 12.8% (19/149), 62.6% (57/91) and 87.4% (104/119) for reader 1 and 2.1% (9/424), 13.6% (20/147), 67.6% (71/105) and 86.3% (88/102) for reader 2, respectively. The areas under the ROC curves for the differentiation of benign and malignant masses were 0.929 and 0.923, respectively; the sensitivity, specificity and accuracy of diagnosis were 85.6% (161/188), 91.7% (541/590), and 90.2% (702/778) for reader 1 and 84.6% (159/188), 91.9% (542/590), and 90.1% (701/778) for reader 2, respectively. Tumours of borderline malignancy or low malignant potential had a higher rate of misclassification (46.1%) than other malignant tumours (6-7.4%). CONCLUSION: The ADNEX MR SCORING system was highly accurate in differentiating benign and malignant adnexal masses, although it may be less accurate for tumours of borderline malignancy or low malignant potential.

Effects of the ether oxygen atom in alkyl side chains on the physical properties of piperidinium ionic liquids.

Various types of piperidinium ionic liquids (ILs) equipped with an oxygen atom-containing alkyl side chain on the positively charged nitrogen atom were systematically synthesized and their physical properties investigated. The thermal stability, viscosity, electrochemical window, and ion conductivity were influenced significantly by changing the position of the oxygen atom in the alkyl chain. Although the lowest viscosity was recorded for 1-((2-methoxyethoxy)methyl)-1-methylpiperidin-1-ium bis(trifluoromethylsulfonyl)amide ([PP1MEM][Tf2N]), 1-methyl-1-(2-propoxyethyl)piperidin-1-ium bis(trifluoromethylsulfonyl)amide ([PP1PE][Tf2N]) can be recommended as the best IL as an electrolyte due to its low viscosity and high thermal and electrochemical stability among the seven ILs tested.