A single arm Phase I/II trial on the combination of carboplatin, nab-paclitaxel and avastin as first-line treatment for advanced non-squamous non-small cell lung cancer (TORG1424/OLCSG1402: CARNAVAL).

BACKGROUND: Bevacizumab with platinum doublet therapy including paclitaxel + carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel + carboplatin led to Grade > 3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination in a Japanese population. METHODS: Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6 cycles of carboplatin (area under the concentration-time curve = 6 on Day 1) + nanoparticle albumin-bound paclitaxel (100 mg/m2 on Days 1, 8 and 15) + bevacizumab (15 mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel + bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. RESULTS: The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42 months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade ≥ 3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). CONCLUSIONS: All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

Impact of Travel Distance on Surgical Outcomes of Patients Surgically Treated for Non-Small Cell Lung Cancer: A Single-Center Study in Ehime, Japan.

Travel burden is a poor prognostic factor for many cancers worldwide because it hinders optimal diagnosis and treatment planning. Currently, the impact of travel burden on survival after surgery for non-small cell lung cancer (NSCLC) in Japan is largely unexplored. We examined the impact of travel distance on the postoperative outcomes of patients with NSCLC in Ehime Prefecture, Japan. The data of 1212 patients who underwent surgical resection for NSCLC were retrospectively reviewed. Patients were divided into quartiles based on the travel distance from their home to the hospital (≤ 13 km, 13-40 km, 40-57 km, and > 57 km) in Ehime Prefecture. We found no significant differences among the quartiles in baseline clinicopathological characteristics, including sex, smoking status, histology, surgical procedure, clinical stage, and pathological stage. Overall survival (OS) and relapse-free survival (RFS) also were not significantly different among the travel distance quartiles. We conclude that travel distance did not impact OS or RFS among patients with NSCLC who underwent surgical resection at our institution.

Trends in patients' behavior for cancer care and the number of registered cancer cases in Ehime Prefecture during the coronavirus disease pandemic.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has reduced diagnosed cancer cases worldwide. This study aimed to elucidate the recovery of cancer care from the COVID-19 pandemic in Ehime Prefecture, Japan. METHODS: This study collected data from the hospital-based cancer registry (HBCR) as well as the number of outpatients, medical information provision fee payments (MIP2) and second opinion patients (SOP) from the Council of Ehime Cancer Care Hospitals (ECCH). Then cancer care and patient requests for hospital transfers before and during the COVID-19 pandemic were analysed. RESULTS: The HBCR from the ECCH comprises >80% of cancer cases in Ehime Prefecture. In 2020, the numbers of all registered cases, first-line treatment cases and cases detected by cancer screening in the HBCR decreased from those in 2018-2019. In 2021, they increased to almost the same levels as those in 2020. In contrast, the number of registered patients that changed hospitals (hospital-change cases) after first-line treatments, patients who lived outside the metropolitan area of Ehime but registered in metropolitan hospitals, MIP2 and SOP remained low in 2021 after decreasing in 2020. Furthermore, the monthly numbers of hospital-change cases, MIP2 and SOP were significantly smaller in 2021 than in 2018-2019 (Wilcoxon rank sum test). CONCLUSIONS: The assessed indicators suggest that the decreased patients' behavior to further cancer care had not returned to pre-pandemic levels by 2021. Hence, psychological measures in society to prevent self-restraint in patients and support for the caregivers of the patients who have some problems visiting the hospital are necessary.

Radical prostatectomy trends between 2010 and 2020 in Ehime, Japan, identified using data from the Medical Investigation Cancer Network (MICAN) study.

OBJECTIVES: The use of radical prostatectomy is increasing with the rising incidence of prostate cancer. We assessed the surgical trends related to radical prostatectomy using data from a multi-center, retrospective cohort study, the MICAN (Medical Investigation Cancer Network) study, which was conducted in all the urology-related medical facilities in Ehime Prefecture, Japan. METHODS: We compared data from the MICAN study with prostate biopsy registry data collected in Ehime between 2010 and 2020 and recorded the surgical trends. RESULTS: There was a significant increase in the mean age of patients with positive biopsies, and the positivity rate increased from 46.3% in 2010 to 60.5% in 2020, while the number of biopsies obtained decreased. The number of radical prostatectomies performed increased over the years, with robot-assisted radical prostatectomy becoming the predominant procedure. In 2020, robot-assisted radical prostatectomies accounted for 96.0% of the surgeries performed. The age at surgery also gradually increased. Of the registered patients aged ≤75 years, 40.5% underwent surgery in 2010, compared with 83.1% in 2020. The prevalence of surgery also increased from 4.6% to 29.8% in patients aged >75 years. There was a gradual increase in the proportion of high-risk cases, from 29.3% to 44.0%, but a decrease in that of low-risk cases, from 23.8% in 2010 to 11.4% in 2020. CONCLUSIONS: We have shown that the number of radical prostatectomies performed in Ehime is increasing in patients aged both ≤75 and >75 years. The proportion of low-risk cases has decreased, while that of high-risk cases has increased.

Nanoparticle albumin-bound paclitaxel and ramucirumab versus paclitaxel and ramucirumab as second-line chemotherapy for unresectable advanced or recurrent gastric cancer: a multicenter, propensity score-matched analysis (CROSS SELL study).

BACKGROUND: Paclitaxel plus ramucirumab (PTX + RAM) is the standard second-line chemotherapy for unresectable advanced or recurrent gastric cancer (AGC). Nanoparticle albumin-bound paclitaxel (nab-PTX) is an improved, more convenient form of PTX and is non-inferior to PTX. Although some retrospective and single-arm phase II studies regarding nab-PTX + RAM have been reported, comparative studies are lacking. Here, we compared the efficacy and toxicity of nab-PTX + RAM and PTX + RAM using propensity score matching. METHODS: Clinical data of 265 patients treated for AGC with nab-PTX + RAM or PTX + RAM were retrospectively collected. Nab-PTX was administered at dosages of 100 mg/m2, replacing PTX in the standard PTX + RAM regimen. Progression-free survival (PFS), overall survival (OS), and toxicity were compared using 1:1 propensity score matching. RESULTS: In total, 190 (72%) patients were matched. The median PFS was 5.3 [95% confidence interval (CI) 4.4-6.3] and 4.7 (95% CI 3.2-5.3) months in the nab-PTX + RAM and PTX + RAM groups, respectively [hazard ratio (HR) = 0.76, 95% CI 0.56-1.03, p = 0.07]. The median OS was 11.5 (95% CI 9.2-15.0) and 9.9 (95% CI 8.0-12.7) months, respectively (HR = 0.78, 95% CI 0.56-1.07, p = 0.12). Grade 3 and 4 neutropenia was observed more frequently in the nab-PTX + RAM group (72% vs. 56%, p = 0.03). No treatment-related deaths occurred. CONCLUSIONS: Nab-PTX + RAM exhibited more favorable trends in terms of PFS and OS but was more myelosuppressive than PTX + RAM. As neutropenia is commonly manageable toxicity, nab-PTX + RAM presents a treatment alternative for AGC. Further studies including randomized, controlled studies are warranted.

Efficacy and Safety of Three-dimensional Conformal Radiotherapy for Macroscopic Vascular Invasion of Hepatocellular Carcinoma.

Chemotherapy is insufficient to treat macroscopic vascular invasion (MVI) of hepatocellular carcinoma (HCC). We retrospectively investigated the treatment outcomes of patients who underwent three-dimensional conformal radiotherapy (3D-CRT) for HCC MVI and analyzed prognostic factors by multivariate analysis using a Cox proportional hazard model. Sixty-five patients were studied. MVI sites were the portal vein (n=48 patients), portal and hepatic veins (n=8), and hepatic vein (n=9). The median irradiation dose was 50 Gy. The median survival time (MST) was 7.5 months. Performance status 2 or 3, modified albumin-bilirubin grade 2b or 3, and massive/diffuse type were poor prognostic factors. Nineteen patients (29%) with a treatment effect of 3 or 4 (≥ 50% of tumor necrosis or regression) at the irradiation sites according to the Response Evaluation Criteria in Cancer of the Liver showed longer survival than those with an effect of 1 or 2 (MST 18.7 vs. 5.9 months, p<0.001). No treatment-related death occurred. The hepatic function reserve was preserved in more than 70% of patients. 3D-CRT controlled HCC MVI safely and was suggested to be a good treatment option.

Risk factors of impairment of shoulder function after axillary dissection for breast cancer.

OBJECTIVES: Postoperative shoulder joint dysfunction has been observed at a certain rate after breast cancer surgery with axillary lymph node dissection. The purposes of this study were to verify the feasibility and effects of home-based exercise using a DVD and clarify the target of intensive intervention with physiotherapy by identifying the factors that cause postoperative shoulder dysfunction. METHODS: The study comprised 237 female patients who underwent breast cancer surgery with axillary lymph node dissection, whose data were acquired until 3 months postoperatively. All patients were instructed to exercise at home using a DVD. Range of motion (ROM) of shoulder flexion and abduction and the disability of the arm, shoulder, and hand (DASH) score were measured before surgery, 1 week and 1, 2, and 3 months after surgery. As factors influencing the recovery of shoulder ROM at 3 months after surgery, the presence or absence of radiation and factors up to 1 month after surgery (age, body mass index, the relationship between operated side and dominant side of the hand, treatment modalities, and complications). RESULTS: Shoulder ROM and DASH scores had gradually recovered from 1 week to 3 months postoperatively. As the results of the multivariate analysis, the factors that were associated with the recovery of ROM of shoulder flexion at 3 months were the side of surgery corresponding to the dominant hand (negative factor) and the presence of paresthesia at 1 week postoperatively (positive factor) (p < 0.05). Radiation therapy and the side of surgery corresponding to the dominant hand were negative factors for the recovery of shoulder abduction (p < 0.01). Regarding the feasibility of the home exercise, 214/229 (93.4%), 172/210 (81.9%), and 139/206 (67.5%) of patients performed exercise at least once a day at 1, 2, and 3 months after surgery, respectively. CONCLUSION: Our result indicated that the side of surgery corresponding to the dominant hand was the inhibiting factor for recovery for both shoulder flexion and abduction at 3 months after surgery. Home-based exercise with DVD was considered feasible. For the verification of this effectiveness, a randomized control study should be planned in the future.

Quality of life after partial lung resection with uniportal versus 3-port video-assisted thoracoscopic surgery: a prospective randomized controlled study.

PURPOSE: The effect of uniportal video-assisted thoracoscopic surgery (uni-VATS) versus that of conventional VATS on postoperative quality of life (QOL) is unclear. This prospective randomized controlled study compared uni-VATS and conventional 3-port VATS in terms of QOL and patient satisfaction. METHODS: The subjects of this study were 84 patients with pulmonary nodules or bullous formation, randomized to undergo uniportal or conventional 3-port video-assisted thoracoscopic partial lung resection. The primary endpoint was postoperative pain, assessed using a numeric rating scale on postoperative day (POD) 1. RESULTS: No differences were found in the numeric rating scale on POD 1 after uni-VATS and conventional 3-port VATS. There were also no differences in blood loss, operative time, complication rate, surgical margin, analgesic requirement, vital capacity (VC), forced expiratory volume in 1 s (FEV1), the 6-min walk test (6MWT), C-reactive protein (CRP) levels, white blood cell count (WBC), or duration of chest tube drainage and hospital stay. Differences were found in the numeric rating scale on days 2, 3, 5, and 10 and in the patient satisfaction score on PODs 5 and 10. CONCLUSIONS: Uni-VATS is associated with less chest pain and better patient satisfaction in the short term but without differences in complication rates or surgical margins from the lesions. CLINICAL TRIAL REGISTRY NUMBER: University Hospital Medical Information Network Clinical Trial Registry (UMIN000015340 http://www.umin.ac.jp/english/ ).

Clinical status and prognostic factors in Japanese patients with uterine leiomyosarcoma.

OBJECTIVE: Uterine leiomyosarcoma (uLMS) is a rare gynecologic malignancy for which the currently available treatments do not consistently provide long-term disease control. This study aimed to reveal the current clinical status of uLMS to support future clinical trials. METHODS: This study enrolled patients with uLMS treated at 53 Japanese institutions from 2000 to 2012. Central pathological review (CPR) was performed. All cases were confirmed by CPR, and epidemiological features, treatment, and prognosis were analyzed statistically. RESULTS: A total of 307 patients were enrolled. A diagnosis of uLMS was confirmed in 266 patients (86.6%) of patients after CPR, of whom data for 259 were analyzed. Of these, 186 (71.8%) patients underwent complete gross resection as primary therapy. Ninety-eight patients received no additional adjuvant therapy, while docetaxel and gemcitabine was the most frequent regimen among 155 patients treated with adjuvant chemotherapy. In all cases, the median overall survival (OS) was 44.2 months. Multivariate analyses of prognostic factors in all cases identified stage III and IV disease, high serum lactate dehydrogenase level, and menopausal status as poor prognostic factors. However, in stage I cases, high serum lactate dehydrogenase level and no adjuvant treatment were identified as poor prognostic factors. The 5-year OS of patients with stage I uLMS treated with adjuvant chemotherapy was significantly better than that of those without adjuvant treatment (67.8% vs 46.7%, P = 0.0461). CONCLUSIONS: Despite complete removal of the primary lesion, the clinical course of patients with uLMS was poor due to recurrence of distant metastasis. The application of a suitable biomarker and effective adjuvant chemotherapy are required to improve the prognosis of patients with uLMS.

Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases.

BACKGROUND: To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. METHODS: The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). RESULTS: The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). CONCLUSIONS: Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.

Late iodine enhancement computed tomography with image subtraction for assessment of myocardial infarction.

OBJECTIVE: To evaluate the feasibility of image subtraction in late iodine enhancement CT (LIE-CT) for assessment of myocardial infarction (MI). METHODS: A comprehensive cardiac CT protocol and late gadolinium enhancement MRI (LGE-MRI) was used to assess coronary artery disease in 27 patients. LIE-CT was performed after stress CT perfusion (CTP) and CT angiography. Subtraction LIE-CT was created by subtracting the mask volume of the left ventricle (LV) cavity from the original LIE-CT using CTP dataset. The %MI volume was quantified as the ratio of LIE to entire LV volume, and transmural extent (TME) of LIE was classified as 0%, 1-24%, 25-49%, 50-74% or 75-100%. These results were compared with LGE-MRI using the Spearman rank test, Bland-Altman method and chi-square test. RESULTS: One hundred twenty-five (29%) of 432 segments were positive on LGE-MRI. Correlation coefficients for original and subtraction LIE-CT to LGE-MRI were 0.79 and 0.85 for %MI volume. Concordances of the 5-point grading scale between original and subtraction LIE-CT with LGE-MRI were 75% and 84% for TME; concordance was significantly improved using the subtraction technique (p <0.05). CONCLUSION: Subtraction LIE-CT allowed more accurate assessment of MI extent than the original LIE-CT. KEY POINTS: • Subtraction LIE-CT allows for accurate assessment of the extent of myocardial infarction. • Subtraction LIE-CT shows a close correlation with LGE-MRI in %MI volume. • Subtraction LIE-CT has significantly higher concordance with TME assessment than original LIE-CT.

Early response assessment of palliative conventional radiotherapy for painful uncomplicated vertebral bone metastases.

BACKGROUND: Radiation therapy (RT) is the common treatment for painful vertebral bone metastases without paralysis by malignant spinal cord compression. However, no studies have focused on the time course of pain after RT. Then, we investigated the change of pain after RT for painful vertebral bone metastases without paralysis. METHODS: Participants included 101 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. All patients received RT and pain response was evaluated by Numeric Rating Scale (NRS). Follow-up assessments were performed just before the start of RT and every month for six months after RT. Pain response was classified as complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) based on the response criteria of International Bone Metastases Consensus Working Party. Responders were classified as either CR or PR, and non-responders as either PP or IR. RESULTS: Median NRS scores for pain were 5 before RT, decreasing to 0 by one month after RT and remaining zero until last follow-up, representing a significant decrease over time (P < 0.001). The rate of responders at each month from one to six months was 93, 96, 95, 100, 98, and 96%, respectively. Multivariate analysis revealed that Spinal Instability Neoplastic Score (SINS) was the only risk factor for response to RT at one month. At one month pain disappeared in 88% of the patients with spinal stability (SINS < 7), although pain disappeared 58% of the patients with spinal instability (SINS ≥ 7), which was significant (P = 0.002). CONCLUSIONS: Pain decreased significantly over time and 93% of patients were classified as responders as early as one month after RT in patients with painful vertebral bone metastases without paralysis. Pretreatment SINS could be a predictor of pain response to RT.

Synthesis of a 1,2-Dithienylethene-Containing Donor-Acceptor Polymer via Palladium-Catalyzed Direct Arylation Polymerization (DArP).

This paper reports the synthesis of D-A polymers containing 1,2-dithienylethene (DTE) units via palladium-catalyzed direct arylation polymerization (DArP). The reaction of dibromoisoindigo (1-Br) and DTE (2-H), in the presence of Pd2(dba)3·CHCl3 (0.5 mol%), P(2-MeOC6H4)3 (L1) (2 mol%), pivalic acid (1 equiv) as catalyst precursors, and Cs2CO3 (3 equiv) as a base affords poly(1-alt-2) with a high molecular weight (Mn up to 44,900). Although, it has been known that monomers, with plural C⁻H bonds, tend to form insoluble materials via direct arylation at undesirable C⁻H positions; the reaction of 1-Br and 2-H cleanly proceeds without insolubilization. The resulting polymer has a well-controlled structure and exhibits good charge transfer characteristics in an organic field-effect transistor (OFET), compared to the polymer produced by Migita⁻Kosugi⁻Stille cross-coupling polymerization. The DArP product displays an ideal linear relationship in the current⁻voltage curve, whereas the Migita⁻Kosugi⁻Stille product shows a VG-dependent change in the charge mobility.

The effect of blood pressure on non-invasive fractional flow reserve derived from coronary computed tomography angiography.

OBJECTIVES: The aim of this study is to assess the effect of blood pressure (BP) on coronary computed tomography angiography (CTA) derived computational fractional flow reserve (CTA-FFR). MATERIALS AND METHODS: Twenty-one patients who underwent coronary CTA and invasive FFR were retrospectively identified. Ischemia was defined as invasive FFR ≤0.80. Using a work-in-progress computational fluid dynamics algorithm, CTA-FFR was computed with BP measured before CTA, and simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg respectively. Correlation between CTA-FFR and invasive FFR was assessed using Pearson test. The repeated measuring test was used for multiple comparisons of CTA-FFR values by simulated BP inputs. RESULTS: Twenty-nine vessels (14 with invasive FFR ≤0.80) were assessed. The average CTA-FFR for measured BP (134 ± 20/73 ± 12 mmHg) was 0.77 ± 0.12. Correlation between CTA-FFR by measured BP and invasive FFR was good (r = 0.735, P < 0.001). For simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg, the CTA-FFR increased: 0.69 ± 0.13, 0.73 ± 0.12, 0.75 ± 0.12, 0.77 ± 0.11, 0.79 ± 0.11, and 0.81 ± 0.10 respectively (P < 0.05). CONCLUSION: Measurement of the BP just before CTA is preferred for accurate CTA-FFR simulation. BP variations in the common range slightly affect CTA-FFR. However, inaccurate BP assumptions differing from the patient-specific BP could cause misinterpretation of borderline significant lesions. KEY POINTS: • The blood pressure (BP) affects the CTA-FFR computation. • Measured BP before CT examination is preferable for accurate CTA-FFR simulation. • Inaccurate BP assumptions can cause misinterpretation of borderline significant lesions.

Risk stratification for predicting symptomatic skeletal events (SSEs) in breast cancer patients with bone metastases.

BACKGROUND: Symptomatic skeletal events (SSEs) affect many patients with bone metastases from breast cancer. However, predictive models of SSEs in patients with bone metastases from breast cancer have not been established for clinical use. The purpose of this study is to examine risk factors for SSEs in those patients and by combining these risk factors patients are classified into several groups. With this risk-stratification model, we can identify patients at higher risk of SSEs and require close follow-up to maintain ADL. METHODS: Participants included 189 female patients with bone metastases from breast cancer and treated in our institute between 2009 and 2012. To assess risk factors for the first SSEs, clinical data at the time of registration were assessed. To estimate the effects of covariates, we used cause-specific hazard modeling. RESULTS: Multivariate analysis revealed that a high number of metastasized vertebral bodies (≥20) (p < 0.001) and elevated carcinoembryonic antigen (CEA) level (>5 ng/mL) (p = 0.003) were risk factors for SSEs. Patients were classified into four subgroups according to the combination of the number of vertebral metastases and CEA level: patients with CEA level > 5 ng/mL and ≥20 vertebral metastases; patients with CEA level ≤ 5 ng/mL and ≥20 vertebral metastases; patients with CEA level > 5 ng/mL and <20 vertebral metastases; and patients with CEA level ≤ 5 ng/mL and <20 vertebral metastases. Cumulative incidences of SSEs in these four subgroups at 6 months were 35.6%, 15.6%, 9.3%, and 3.7%, respectively. CONCLUSIONS: Patients with elevated CEA level (>5 ng/mL) and extensive vertebral metastases (≥20) should be closely monitored in routine clinical care, to allow prevention of pathological fracture or paraplegia with the intervention of orthopedists or radiologists.

The incidence of atypical femoral fractures in breast cancer patients with bone metastases who received bisphosphonate treatment.

BACKGROUND: Atypical femoral fractures (AFFs) have been reported to occur in patients with bone metastases who received long-term bisphosphonate treatment. However, the incidence of AFFs in breast cancer patients with bone metastases who received intravenous bisphosphonate is unclear. The purpose of this study is to examine the incidence of AFFs in breast cancer patients with bone metastases who received intravenous bisphosphonate. In addition, we estimated the number of dose and duration of intravenous bisphosphonate at the time of occurrence of AFFs. METHODS: We identified 356 female breast cancer patients with bone metastases who received intravenous bisphosphonate between November 2004 and October 2013 in our institution. The median number of doses of intravenous bisphosphonate was 18 (range, 1-103). The median duration of intravenous bisphosphonate treatment was 16 months (range, 1-102 months). We estimated the incidence of AFFs in patients who received intravenous bisphosphonate and used Poisson regression model to obtain the incidence rates of AFFs. RESULTS: Three AFFs in two patients were identified and the estimated incidence of AFFs was 2.99 per 1000 person-years. At the time of occurrence of AFFs, the patients had received 41 and 83 doses of intravenous bisphosphonate, for 37 and 79 months, respectively. The patients underwent open reduction and internal fixation with intramedullary nail. The frequency and incidence of AFFs in patients who received intravenous bisphosphonate for at least 41 or 83 doses or for more than 37 or 79 months were 2/60 (3.3%), 1/7 (14.3%), 2/70 (2.9%), and 1/9 (11.1%), respectively. CONCLUSIONS: The incidence of AFFs is low in breast cancer patients with bone metastases who received intravenous bisphosphonate. Careful observation is warranted and radiography should be performed to investigate AFFs when clinical signs such as thigh pain appear. STUDY DESIGN: Clinical study.

Significance of metacognitive skills in laparoscopic surgery assessed by essential task simulation.

BACKGROUND: Metacognition is the knowledge about one's own methods of perceiving, remembering, thinking, and acting. This study determined the significance of metacognitive skills in laparoscopic surgery with the aim of applying the findings in a laparoscopic surgery training program. MATERIAL AND METHODS: Eighteen medical students with no experience in laparoscopic surgery (novice group) and eight expert surgeons who had each performed >100 laparoscopic surgeries (expert group) were enrolled. The examinees in each group performed an evaluation task using a virtual reality simulator and answered questions about the task. RESULTS: The longest performance times, longest path lengths, and most frequent tissue damage occurred at 135° in the novice group and at 180° in the expert group. The greatest recognition of task difficulties, impatience, and irritation occurred at 135° in the novice group and at 180° in the expert group. There were statistically significant correlation coefficients between the instrument path length and task difficulty (metacognition) at 135° (R = 0.74, p = 0.03) and 180° (R = 0.79, p = 0.02) in the expert group, but there were no significant correlations in the novice group. CONCLUSION: We elucidated the significance of metacognitive skills in laparoscopic surgery. A training program should include recognition feedback systems.

VAMP5 promotes Fcγ receptor-mediated phagocytosis and regulates phagosome maturation in macrophages.

Phagosome formation and maturation reportedly occur via sequential membrane fusion events mediated by synaptosomal-associated protein of 23 kDa (SNAP23), a plasma membrane-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family. Vesicle-associated membrane protein 5 (VAMP5), also a plasmalemma SNARE, interacts with SNAP23; however, its precise function in phagocytosis in macrophages remains elusive. To elucidate this aspect, we investigated the characteristics of macrophages in the presence of VAMP5 overexpression or knockdown and found that VAMP5 participates in Fcγ receptor-mediated phagosome formation, although not directly in phagosome maturation. Overexpressed VAMP5 was localized to the early phagosomal membrane but no longer localized to the lysosomal-associated membrane protein 1-positive maturing phagosomal membrane. Analyses using compound-based selective inhibitors demonstrated that VAMP5 dissociation from early phagosomes occurs in a clathrin- and dynamin-dependent manner and is indispensable for SNAP23 function in subsequent membrane fusion during phagosome maturation. Accordingly, to the best of our knowledge, we demonstrate, for the first time, that VAMP5 exerts an immunologically critical function during phagosome formation and maturation via SNARE-based membrane trafficking in macrophages.

Perioperative Anaphylaxis in Japanese Secondary Care Institutions: Incidence, Causes, and the Imperative for Improved Diagnostic Practices.

Background This research investigates the incidence, suspected causes, and diagnostic procedures for perioperative anaphylaxis (POA), a potentially severe complication, in secondary care hospitals across Japan. Methodology We surveyed Saiseikai hospitals and gathered data on surgical procedures, POA occurrences, potential triggers, and diagnostic methods. Results Among 70,523 surgeries, seven were associated with POA, resulting in an approximate incidence rate of 0.01%. Rocuronium was the most commonly suspected trigger, followed by sugammadex, latex, and angiography contrast agents. Despite the importance of skin tests as the most basic and crucial diagnostic method, they were conducted in only three instances. No in vitro tests for drug identification were conducted, and in four cases, the cause was determined merely based on the timing of drug administration, indicating significant diagnostic limitations. Conclusions The study underscores the critical situation in Japan regarding insufficient diagnostic practices and difficulties in identifying triggering drugs rather than the consistent prevalence of POA in secondary care facilities. The findings emphasize the need for improved diagnostic proficiency and more rigorous drug identification practices to ensure prompt and accurate POA diagnosis. It is essential to conduct further research and interventions to increase patient safety during the perioperative period in secondary care settings.

Impact of timing of radium­223 administration on the survival of patients with bone metastatic castration­resistant prostate cancer.

The present study aimed to evaluate the optimal timing of radium-223 chloride (Ra-223) administration among patients with bone metastasis from castration-resistant prostate cancer (BmCRPC). Patients, who were diagnosed with BmCRPC and treated with Ra-223 therapy between October, 2016 and January, 2022, were reviewed. The survival time was calculated from the initiation of Ra-223 administration. The time from the diagnosis of BmCRPC to the initiation of Ra-223 administration was identified as a potential prognostic factor. A total of 51 patients were examined in the present study. Ra-223 was administered as the first- and second-line therapy (earlier Ra-223 administration) in 32 patients and as the third- to fifth-line therapy (later Ra-223 administration) in 19 patients. In the multivariate analysis, which considered the potential prognosis, the difference in survival times between patients who received early and late Ra-223 administration was not significant [hazard ratio (HR), 2.67; 95% confidence interval (CI), 0.79-9.07; P=0.11]. By contrast, an incomplete Ra-223 administration (HR, 128.03; 95% CI, 10.59-1548.42; P<0.01) and higher levels of prostate-specific antigen prior to Ra-223 administration (HR, 7.86; 95% CI, 2.7-27.24; P<0.01) were independent factors, significantly associated with a poorer prognosis. The timing of Ra-223 administration did not significantly affect the survival of patients from the initiation of treatment. Further studies are thus required to determine the optimal timing for Ra-223 administration.