Prognostic significance of C-reactive protein in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

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.

[A case of secondary sclerosing cholangitis following endoscopic submucosal dissection ulcer bleeding].

A 75-year-old male patient underwent endoscopic submucosal dissection (ESD) for early gastric cancer. The ESD ulcer bleeding occurred 7 days post-ESD, and he underwent endoscopic clipping hemostasis. Afterward, the patient presented with acute cholecystitis and cholangitis, thereby developing sclerosing cholangitis. His hepatic failure worsened and he died 15 months post-ESD although we performed endoscopic dilations for bile duct stenosis and administered antibiotics. We considered the condition to be related to secondary sclerosing cholangitis in critically ill patients (SSC-CIP) caused by bile duct ischemia and cholangitis.

[A case of chronic hepatitis B managed with continued adefovir despite treatment-related Fanconi syndrome and osteomalacia].

A 64-year-old woman was prescribed lamivudine and adefovir (ADV) for chronic hepatitis B. Although her serum creatinine level was normal (<1.01 mg/dl), she developed bone pain due to Fanconi syndrome and osteomalacia. Therefore, ADV was discontinued and she was switched to entecavir (ETV); however, she developed an ETV-resistant mutant virus and a small dose of ADV was restarted. Her hepatitis B virus (HBV) -DNA levels and renal function were closely monitored. She has had preserved creatinine levels and tubular function, with almost undetectable HBV-DNA levels for more than a year after treatment.

Combination of extractive solvent addition and immobilization culture for continuous production of scopoletin by tobacco cells.

Extractive solvent addition was combined with immobilization cultures of Nicotiana tabacum cells to produce scopoletin. Using various solvents, the partition coefficients of scopoletin between the solvent and water phases and the solvent toxicity to the cell viability were investigated. The effect of the solvent addition on cell growth and scopoletin production was elucidated in the suspension cultures. Coconut oil, one of the natural vegetable oils, was selected as the most suitable extractive solvent. The cells were immobilized in the calcium alginate gel bead coated with a cell-free gel film and then the batch cultures with the addition of various volumes of the coconut oil were performed. The total scopoletin production increased with the solvent volume according to the amount of scopoletin transferred from the medium to the solvent. The maximum productivity obtained in the batch immobilization cultures was about 16 times larger than that in the suspension culture without solvent. A continuous production system, in which the fresh solvent was supplied to the culture system and the solvent containing scopoletin was recovered from it, was constructed. The integrated scopoletin production in the effluent oil attained 2.21 mg/gDCW for 30 days at 100 cm(3)/day without cell leakage.