Current status of the cost burden of first-line systemic treatment for patients with advanced hepatocellular carcinoma in Japan, 2021-22.

BACKGROUND: Although recent advances in systemic therapies for hepatocellular carcinoma (HCC) have led to prolonged patient survival, the high costs of the drugs place a heavy burden on both patients and society. The objectives of this study were to examine the treatment regimens used as first-line systemic treatment for patients with advanced HCC in Japan and to estimate the treatment costs per regimen. METHODS: For this study, we aggregated the data of patients who had received first-line systemic treatment for advanced HCC between July 2021 and June 2022. The treatment cost per month of each regimen was estimated based on standard usage, assuming an average weight of 60 kg for male patients. The data were categorized by the treatment regimen, and the treatments were categorized based on the cost into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month) and other (<500 000 JPY/month) treatments. RESULTS: Of the total of 552 patients from 24 institutions whose data were analyzed in this study, 439 (79.5%) received atezolizumab plus bevacizumab, 98 (17.8%) received lenvatinib and 15 (2.7%) received sorafenib as the first-line treatment. The treatment cost per month for each of the above regimens was as follows: atezolizumab plus bevacizumab, 1 176 284 JPY; lenvatinib, 362 295 JPY and sorafenib, 571 644 JPY. In total, 82.2% of patients received high-cost regimens, and the majority of these patients received a very high-cost regimen of atezolizumab plus bevacizumab. CONCLUSIONS: Advances in systemic therapies for HCC have led to prolonged patient survival. However, the treatment costs are also increasing, imposing a burden on both the patients and society.

A clinical assessment of portable point-of-care testing for quick cortisol assay during adrenal vein sampling.

This study assessed the clinical performance of point-of-care testing (POCT) for quick cortisol assay (QCA) during adrenal vein sampling (AVS) using a newly invented portable quantitative assay instrument. An observational study was conducted prospectively at two centres in Japan. Forty-eight patients with primary aldosteronism considered for adrenalectomy were enrolled in this study and underwent AVS. Three basal adrenal vein samples from each adrenal vein and two from the inferior vena cava were collected sequentially. The cortisol concentration of adrenal vein samples was measured by routine method and QCA. A total of 338 adrenal vein samples were analysed from 250 sites to determine AVS success or failure. The distribution of turnaround time of the QCA for AVS success or failure followed a normal distribution with an average of 20.5 min. A positive correlation between the routine method and QCA was observed regarding cortisol concentration or selectivity index. No significant difference between the two methods was observed regarding the success rate of AVS. Using the routine method as a reference, the sensitivity and specificity of AVS success or failure were 99.1% (210/212) and 81.6% (31/38), respectively. Easy, quick, portable, and precise POCT-QCA demonstrated its compatibility with routine methods regarding clinical performance.

Forecasting the seasonal pollen index by using a hidden Markov model combining meteorological and biological factors.

The seasonal pollen index (SPI) is a continuing concern within the fields of aerobiology, ecology, botany, and epidemiology. The SPI of anemophilous trees, which varies substantially from year to year, reflects the flowering intensity. This intensity is regulated by two factors: weather conditions during flower formation and the inner resource for assimilation. A deterministic approach has to date been employed for predicting SPI, in which the forecast is made entirely by parameters. However, given the complexity of the masting mechanism (which has intrinsic stochastic properties), few attempts have been made to apply a stochastic model that considers the inter-annual SPI variation as a stochastic process. We propose a hidden Markov model that can integrate the stochastic process of mast flowering and the meteorological conditions influencing flower formation to predict the annual birch pollen concentration. In experiments conducted, the model was trained and validated by using data in Hokkaido, Japan covering 22 years. In the model, the hidden Markov sequence was assigned to represent the recurrence of mast years via a transition matrix, and the observation sequences were designated as meteorological conditions in the previous summer, which are governed by hidden states with emission distribution. The proposed model achieved accuracies of 83.3% in the training period and 75.0% in the test period. Thus, the proposed model can provide an alternative perspective toward the SPI forecast and probabilistic information of pollen levels as a useful reference for allergy stakeholders.

Assessment of surgical skills by using surgical navigation in robot-assisted partial nephrectomy.

PURPOSE: To assess surgical skills in robot-assisted partial nephrectomy (RAPN) with and without surgical navigation (SN). METHODS: We employed an SN system that synchronizes the real-time endoscopic image with a virtual reality three-dimensional (3D) model for RAPN and evaluated the skills of two expert surgeons with regard to the identification and dissection of the renal artery (non-SN group, n = 21 [first surgeon n = 9, second surgeon n = 12]; SN group, n = 32 [first surgeon n = 11, second surgeon n = 21]). We converted all movements of the robotic forceps during RAPN into a dedicated vocabulary. Using RAPN videos, we classified all movements of the robotic forceps into direct action (defined as movements of the robotic forceps that directly affect tissues) and connected motion (defined as movements that link actions). In addition, we analyzed the frequency, duration, and occupancy rate of the connected motion. RESULTS: In the SN group, the R.E.N.A.L nephrometry score was lower (7 vs. 6, P = 0.019) and the time to identify and dissect the renal artery (16 vs. 9 min, P = 0.008) was significantly shorter. The connected motions of inefficient "insert," "pull," and "rotate" motions were significantly improved by SN. SN significantly improved the frequency, duration, and occupancy rate of connected motions of the right hand of the first surgeon and of both hands of the second surgeon. The improvements in connected motions were positively associated with SN for both surgeons. CONCLUSION: This is the first study to investigate SN for nephron-sparing surgery. SN with 3D models might help improve the connected motions of expert surgeons to ensure efficient RAPN.

Modified response evaluation criteria in solid tumors is superior to response evaluation criteria in solid tumors for assessment of responses to sorafenib in patients with advanced hepatocellular carcinoma.

BACKGROUND: Modified response evaluation criteria in solid tumors (mRECIST) and RECIST are used to assess the effect of treatment with targeted agents for hepatocellular carcinoma (HCC). The aim of this study was to determine which set of criteria is superior in patients with advanced HCC treated with sorafenib. METHODS: A multicenter retrospective study to assess the tumor response and patient prognosis of 191 patients with HCC who had been treated with sorafenib from May 2009 through December 2011. We analyzed tumor responses as shown by contrast-enhanced computed tomography scan images according to RECIST 1.1 and mRECIST and compared the findings. RESULTS: The median duration of follow-up was 9.7 months and median overall survival was 10.8 months. Twenty-five patients (13.1 %) were assessed as responders by mRECIST and 15 (7.8 %) by RECIST 1.1. There was a significant difference in overall survival (OS) between responders and non-responders according to mRECIST (P = 0.0117), but no significant difference in OS between responders and non-responders according to RECIST 1.1 (P = 0.0722). Sixteen patients (8.4 %) had no measurable enhanced target lesions that could be assessed as required by mRECIST; however, these patients could be assessed by RECIST 1.1. According to RECIST 1.1, eight of them had stable disease (SD) and eight had progressive disease (PD). There was a significant difference in OS between these SD and PD patients (P = 0.0312). CONCLUSIONS: Patients treated with sorafenib for HCC should be evaluated by mRECIST; RECIST 1.1 is preferable only for assessment of patients with lesions that are non-measurable according to mRESIST.

Assessment of left ventricular ejection fraction measured by quantitative gated SPECT: correlation with left ventriculography and first-pass radionuclide angiography.

PURPOSE: The purpose of this study was to evaluate the reliability of left ventricular ejection fraction (LVEF) measured by quantitative gated SPECT (QGS). We compared the efficacy of LVEF assessment among Tc-99m tetrofosmin gated SPECT imaging, contrast left ventriculography (LVG), and first-pass radionuclide angiography (FP). PATIENTS: One-hundred and seven patients with ischemic heart disease underwent QGS and LVG simultaneously within 3 months, and 92 of the 107 patients also underwent FP at the same time. RESULTS: QGS progressively overestimated LVEF at the lower range of end-systolic volume (ESV), especially in patients with small hearts. Moreover, the QGS technique systemically tended to underestimate LVEF in comparison with LVG. However, linear regression analysis demonstrated a good correlation between the LVEF values measured by QGS and those measured by both LVG (p<0.0001) and FP (p<0.0001). CONCLUSION: Although QGS has a tendency to overestimate LVEF in patients with small hearts, and to systemically underestimate LVEF compared with LVG, this technique is still a reliable clinical tool for measurement of LVEF.