AIM:C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC).METHODS:A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score.RESULTS:Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin-bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313-5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin-bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively.CONCLUSIONS:CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy.

RATIONALE:The small intestine (SI) does not commonly harbor cancer but is occasionally involved by metastatic cancer from other organs. To manage SI cancer appropriately, surveillance for primary origin outside the SI is essential.PATIENT CONCERNS:This study presents a 54-year-old Thai man diagnosed with SI obstruction which required laparoscopy- assisted partial ileal resection.DIAGNOSES:On the basis of the expression pattern of cytokeratins (CKs) and mucins (MUCs) in the resected SI adenocarcinoma, we suspected this was metastasized from the pancreatobiliary tract. Imaging studies revealed a hepatic segmental atrophy with an occlusion of the posterior segmental blanch of the portal vein without any contrast-enhanced lesions in the liver. Pathology of the liver biopsy revealed intrahepatic cholangiocarcinoma (ICC) with the same expression pattern of CKs and MUCs as the SI adenocarcinoma.INTERVENTIONS:Systemic chemotherapy (gemcitabine and cisplatin) was initiated.OUTCOMES:Despite of the chemotherapy for 20 months, he died of ICC.LESSONS:This is the first case of SI obstruction caused by the metastasis of ICC. We demonstrate that immunohistochemical staining of CKs and MUCs discriminate between primary and metastatic SI cancer and predict its primary origin outside the SI. This case also suggests that a hepatic segmental atrophy with portal vein occlusion would be an atypical but important finding to diagnose ICC.

ABSTRACT A lack of patient response to alpha interferon (α-IFN) plus ribavirin (RBV) treatment is a major problem in eliminating hepatitis C virus (HCV). We screened chemical libraries for compounds that enhanced cellular responses to α-IFN and identified a triterpenoid, toosendanin (TSN). Here, we studied the effects and mechanisms of action of TSN on HCV replication and its effect on α-IFN signaling. We treated HCV genotype 1b replicon-expressing cells and HCV-J6/JFH-infected cells with TSN, with or without α-IFN, and the level of HCV replication was quantified. To study the effects of TSN on α-IFN signaling, we detected components of the interferon-stimulated gene factor 3 (ISGF3), phosphorylated signal transducer and activator of transcription 1 (STAT1), and STAT2 by Western blotting analysis; expression levels of mRNA of interferon regulatory factor 9 using real-time reverse transcription-PCR (RT-PCR); and interferon-stimulated response element reporter activity and measured the expression levels of interferon-inducible genes for 2′,5′-oligoadenylate synthetase, MxA, protein kinase R, and p56 using real-time RT-PCR. TSN alone specifically inhibited expression of the HCV replicon (50% effective concentration = 20.6 nM, 50% cytotoxic concentration > 3 μM, selectivity index > 146). Pretreatment with TSN prior to α-IFN treatment was more effective in suppressing HCV replication than treatment with either drug alone. Although TSN alone did not activate the α-IFN pathway, it significantly enhanced the α-IFN-induced increase of phosphorylated STATs, interferon-stimulated response element activation, and interferon-stimulated gene expression. TSN significantly increased baseline expression of interferon regulatory factor 9, a component of interferon-stimulated gene factor 3. Antiviral effects of treatment with α-IFN can be enhanced by pretreatment with TSN. Its mechanisms of action could potentially be important to identify novel molecular targets to treat HCV infection.

症例は36歳女性。先天性胆道拡張症に対して胆管切除，胆管空腸吻合（Roux-en-Y再建）を施行している。術後5年でCT等画像検査にて肝内胆管に腫瘤様陰影をみとめ，悪性疾患の鑑別を目的にダブルバルーン内視鏡を施行したところ胆管空腸吻合部に結石の嵌頓をみとめ肝内結石症と診断した。ダブルバルーン内視鏡は，これまで困難とされてきた術後再建腸管に対する内視鏡的診断・治療に有用であると考えられる。

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.

症例は70歳男性。健診にて胃ポリープを指摘され内視鏡検査を施行し，胃体上部大彎に表面顆粒状で10mm大のIspポリープを認めたが，組織学的に悪性所見を認めなかったため1年間経過観察したところ2003年10月には15mm大へと増大傾向を示し切除目的で入院となった。術前検査にてsm浸潤も否定できなかったが，患者，家族の強い希望によりEMRを施行した。切除標本ではsm2相当の浸潤を伴う乳頭腺癌と診断された。免疫染色にてMUC-5AC・MUC-6陽性，CD10・MUC-2陰性であり，胃型形質を発現している腺癌であった。組織学的には肉眼的境界よりも広く進展していたが，異所性胃粘膜と胃癌の混在した稀な病変と考えられた。 内視鏡所見と組織学的所見が乖離し，今後も慎重な経過観察が必要と考えられた。