川部 直人

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.

はじめに:進行肝細胞癌患者に対してアテゾリズマブ+ベバシズマブ治療を行う際に,尿蛋白定性検査と尿蛋白/クレアチニン比(UPCR)を同時に測定すると結果が解離する症例にしばしば遭遇する。本研究では,アテゾリズマブ+ベバシズマブ治療中の進行肝細胞癌患者における尿蛋白定性検査とUPCRとの関係を調べ,UPCRを尿蛋白のモニタリング時に追加することで,ベバシズマブの不必要な休薬を防ぐことができるかどうかを評価した。対象と方法:2020年10月1日～2021年8月31日までに当院でアテゾリズマブ+ベバシズマブ治療を受けた進行肝細胞癌の61例から採取した延べ298尿検体を対象とした。本研究ではUPCRを1日尿蛋白排泄量と同等として評価し,ベバシズマブの休薬基準をUPCR2.0以上とした。結果:UPCR2.0を超えた検体は尿蛋白定性2+で1/41(2.4%),3+で24/44(54.5%)であった。仮に尿蛋白定性2+で休薬と判断した場合,40/41検体(97.6%)もの場合でベバシズマブの投与を継続することができ,尿蛋白定性3+で休薬を判断した場合でも20/44検体(45.5%)とほぼ半数近くの場合でベバシズマブの投与を継続することができると考えられた。結論:実臨床において,進行肝細胞癌患者に対するアテゾリズマブ+ベバシズマブ治療を行う際に,尿蛋白定性検査にUPCRを追加することはベバシズマブの不必要な休薬を防ぐことができ,尿蛋白定性検査のみを使用する場合に比べて,より多くの臨床的ベネフィットを得ることにつながる可能性があると考えられた。(著者抄録)

INTRODUCTION: When we administer atezolizumab plus bevacizumab treatment to patients with advanced hepatocellular carcinoma, we often encounter inconsistent results between the qualitative dipstick urinalysis and the urine protein/creatinine ratio(UPCR)measurements. In this study, we investigated the relationship between qualitative dipstick urinalysis and UPCR in these patients, and assessed whether incorporating UPCR into the testing protocol could prevent unnecessary interruptions during bevacizumab treatment. SUBJECTS AND METHODS: This study analyzed 298 urine samples collected from 61 patients of advanced hepatocellular carcinoma, who were treated with atezolizumab plus bevacizumab at our institution between October 1, 2020, and August 31, 2021. We used UPCR as an alternative test to the 24-hour urine protein and set the discontinuation criteria for bevacizumab at a UPCR of 2.0 or higher. RESULTS: Among the 41 samples that tested positive for 2+ on the dipstick test, only one(2.4%)had a UPCR exceeding 2.0. Additionally, among the 44 samples that showed a 3+ result, 24 samples(54.5%)had a UPCR higher than 2.0. If our decision to discontinue bevacizumab had been based on a dipstick urinalysis result of 2+, we could have continued administering bevacizumab in 97.6%(40/41)of the cases. Even if the decision had been based on a dipstick urinalysis result of 3+, we could have continued administering bevacizumab in almost half of the cases(45.5%, 20/44). CONCLUSIONS: Our findings suggest that the addition of UPCR to the qualitative dipstick urinalysis during atezolizumab plus bevacizumab treatment for patients with advanced hepatocellular carcinoma could help prevent unnecessary interruptions of bevacizumab and offer more clinical benefits in real-world practice, compared to using qualitative dipstick urinalysis alone.