Impact of telephone follow-up on hepatocellular carcinoma patients receiving oral chemotherapy from an ambulatory-care setting.

INTRODUCTION: In recent years, most molecular target drugs have been administered orally, as prescribed at ambulatory services in hospitals and at patients' homes. Telephone follow-up is increasingly being used in clinical practice for patients needing additional support post-discharge and for the prevention of hospital readmissions. The purpose of this study was to clarify the clinical benefits of telephone follow-up while administering oral anticancer drugs. METHODS: This was a single-center, observational, retrospective study. We evaluated hepatocellular carcinoma patients who received sorafenib or lenvatinib between March 2010 and February 2018. The primary endpoint was the incidence of adverse events. RESULTS: From the total of 130 patients, 83 patients received telephone follow-up and 47 did not. The incidence of hand-foot skin reactions significantly reduced in patients with telephone follow-up (odds ratio (OR) 3.69, 95% confidence interval (CI) 1.16-11.8, p = 0.020). The median durations (ranges) of adherence to oral chemotherapy were 259 days (15-1730) for the telephone follow-up group and 121 days (14-1105) for the no-telephone follow-up group (p < 0.001). Moreover, the disease control rate was significantly higher in the telephone follow-up group (OR 2.52, 95% CI 1.15-5.53, p = 0.020). CONCLUSIONS: Remote interventions, such as telephone follow-up, are useful means of managing adverse events in patients receiving oral anticancer drugs and can lead to improved treatment results.

Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment.

Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; n = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. Conclusion: Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.

Effects of activation of an alcohol metabolic gene, cigarette smoking, and alcohol intake on the incidence of metachronous gastric cancer in patients who underwent endoscopic resection for gastric cancer: A multicenter retrospective pilot study.

Background and Aim: Metachronous gastric cancer (GC) frequently occurs in patients who have undergone endoscopic resection (ER) for GC. We evaluated the risk for development of metachronous GC following ER for GC based on genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2), as well as alcohol consumption and smoking habits. Methods: We studied 77 patients who underwent ER for GC (median follow-up of 84 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. Histories of alcohol consumption and smoking before and after ER and Helicobacter pylori eradication were documented. Results: Multivariate analyses revealed that homozygous slow-metabolizing ADH1B (hazard ratio [HR] = 2.38, P < 0.13), heavy smoking (HR = 2.36, P < 0.09), and cigarette smoking after ER (HR = 2.47, P < 0.10) were not independently associated with the risk of secondary GC development. We analyzed the cessation status of the 38 patients who were classified as heavy smokers before ER based on their smoking habits after the ER and divided them into a cessation group (n = 27, non-smokers after ER) and a non-cessation group (n = 11). Cumulative incidence curves of secondary GC in the cessation and non-cessation groups revealed 5-year incidence rates of 19.0% and 45.0%, respectively (P = 0.02). Conclusion: Continued cigarette smoking, at a high level, may be an important risk factor for the development of metachronous GC. Advice for smoking cessation should be given.

Serum Angiopoietin-2 Predicts the Occurrence and Recurrence of Hepatocellular Carcinoma after Direct-Acting Antiviral Therapy for Hepatitis C.

Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014-2020 were screened and evaluated for HCC occurrence or recurrence every three-six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34-6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18-6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.

Prophylactic tenofovir alafenamide for hepatitis B virus reactivation and reactivation-related hepatitis.

No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing hepatitis B virus (HBV) reactivation has yet been reported. This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF. Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis.

Hepatocellular Carcinoma Rupture after Introducing Lenvatinib: An Autopsy Case Report.

Hepatocellular carcinoma (HCC) hemorrhaging/rupture is a rare adverse effect of lenvatinib, and only limited pathological examinations have been reported. This report presents the case of a 69-year-old man who suffered from cardiac arrest and died 7 days after starting lenvatinib treatment for HCC, with an autopsy subsequently performed. Crack and coagulated blood were observed in the largest tumor. Pathologically, the hemorrhaging area was scattered in nearly all of the HCC lesions, regardless of tumor differentiation. This pathological feature is unusual in normal HCC. Thus, it is believed to have been the effect of lenvatinib.

Antemortem Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy in a Patient with Recurrent Breast Cancer: An Autopsy Case Report.

OBJECTIVE: Herein, we report a case of a patient with recurrent breast cancer who was diagnosed antemortem with pulmonary tumor thrombotic microangiopathy (PTTM) using wedge aspiration cytology of the pulmonary artery after breast cancer surgery. CASE SUMMARY: The patient was a 50-year-old woman who underwent mastectomy and axillary lymph node dissection for stage IIIA (T3N2M0) triple-negative left breast cancer. Postoperative follow-up was performed with radiotherapy and anticancer chemotherapy. Seventeen months after the surgery, the patient was hospitalized for right heart failure and diagnosed with pulmonary arterial hypertension. The patient was diagnosed with PTTM following the detection of malignant cells in the pulmonary artery using wedge aspiration cytology. Anti-pulmonary hypertension therapy was administered; however, the patient did not respond and died 26 days after admission. Autopsy revealed multiple microscopic tumor emboli in the pulmonary artery. In portions of the pulmonary artery without embolization, fibro-cellular intimal hyperplasia and stenosis were observed. Tumor embolism was expressed for CK7+/CK20-, consistent with the primary breast cancer. DISCUSSION: Since the primary pathophysiology of PTTM entails narrowing due to fibro-cellular intimal hyperplasia rather than multiple tumor thrombi, the efficacy of chemotherapy combined with vasodilators is discussed.

Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150.

The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.

Pressure-induced transitions inRCo5(R=Y, La) studied by x-ray emission spectroscopy, x-ray diffraction and density functional theory.

The hydrostatic pressure dependent evolution of the electronic and magnetic structure of LaCo5and YCo5was investigated by means of x-ray emission spectroscopy, x-ray diffraction, and spin-polarized density functional theory (DFT) calculations. Using experimental lattice parameters the DFT correctly predicts the pressure of the magnetic transition in both compounds to be 26 GPa (La) and 22-23 GPa (Y). The transition was experimentally resolved in the changes of the electronic structure via the integrated absolute difference of the CoKßemission spectra. Comparison of theory and experiment confirm for the first time a common feature in both LaCo5and YCo5to be the source of the transition; the Fermi-level crossing of an up-spin polarized flat band driving the systems into a low spin configuration via a Lifshitz type transition of the Fermi surface. Another phase transition observed around 12 GPa in LaCo5was clarified to be caused by the change in the down-spin density of states at the Fermi level.

Very urgent endoscopic retrograde cholangiopancreatography is associated with early

Background: endoscopic retrograde cholangiopancreatography (ERCP) is a first-line procedure for biliary drainage in patients with acute cholangitis, and there are no studies focused on very urgent ERCP within several hours of hospital arrival. This study aimed to elucidate the use of very urgent ERCP for non-severe acute cholangitis.Methods: this retrospective observational study included patients with non-severe acute cholangitis who underwent ERCP between April 2011 and June 2020 in our institution. Patients were stratified into three groups based on time to ERCP after hospital arrival: very urgent (≤ 3 hours), urgent (3-24 hours) and elective (> 24 hours). The primary outcome was length of hospital stay (LOS).Results: the study cohort included 291 patients, 168 males (57.7 %), with a median age of 76 (interquartile range, 70-83) years. In all, 47, 196 and 48 patients underwent very urgent, urgent and elective ERCP, respectively. Median LOS in the very urgent, urgent, and elective groups was 12, 14, and 15 days, respectively (Kaplan-Meier method). A shorter LOS was associated with earlier ERCP (log-rank trend test, p = 0.04). The rates of readmission within 30 days of discharge and of adverse events were not significantly different among the three groups. By multivariate analysis, very urgent ERCP was associated with a significantly earlier discharge than urgent and elective ERCP (HR, 0.71, p = 0.04 and HR, 0.47, p < 0.01, respectively). In addition, age ≥ 75 years, pancreatitis, albumin ≤ 2.8 g/dL and two or more ERCP procedures were associated with a significantly longer LOS (HRs < 1, p < 0.05). (AU)

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B.

For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.

Prediction of hepatocellular carcinoma using age and liver stiffness on transient elastography after hepatitis C virus eradication.

Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age < 71 years and LSM < 8.4 kPa at the time of SVR24, the 4-year cumulative incidence of HCC was as low as 1.1%. Both pre-treatment LSM (≥ 9.2 kPa) and SVR24 LSM (≥ 8.4 kPa) and age (≥ 71 years) are useful in predicting the risk of HCC after SVR with IFN-free treatment. Identification of low-risk individuals may improve the efficiency of follow-up.

Very urgent endoscopic retrograde cholangiopancreatography is associated with early discharge in patients with non-severe acute cholangitis.

BACKGROUND: endoscopic retrograde cholangiopancreatography (ERCP) is a first-line procedure for biliary drainage in patients with acute cholangitis, and there are no studies focused on very urgent ERCP within several hours of hospital arrival. This study aimed to elucidate the use of very urgent ERCP for non-severe acute cholangitis. METHODS: this retrospective observational study included patients with non-severe acute cholangitis who underwent ERCP between April 2011 and June 2020 in our institution. Patients were stratified into three groups based on time to ERCP after hospital arrival: very urgent (≤ 3 hours), urgent (3-24 hours) and elective (> 24 hours). The primary outcome was length of hospital stay (LOS). RESULTS: the study cohort included 291 patients, 168 males (57.7 %), with a median age of 76 (interquartile range, 70-83) years. In all, 47, 196 and 48 patients underwent very urgent, urgent and elective ERCP, respectively. Median LOS in the very urgent, urgent, and elective groups was 12, 14, and 15 days, respectively (Kaplan-Meier method). A shorter LOS was associated with earlier ERCP (log-rank trend test, p = 0.04). The rates of readmission within 30 days of discharge and of adverse events were not significantly different among the three groups. By multivariate analysis, very urgent ERCP was associated with a significantly earlier discharge than urgent and elective ERCP (HR, 0.71, p = 0.04 and HR, 0.47, p < 0.01, respectively). In addition, age ≥ 75 years, pancreatitis, albumin ≤ 2.8 g/dL and two or more ERCP procedures were associated with a significantly longer LOS (HRs < 1, p < 0.05). CONCLUSIONS: very urgent ERCP for non-severe acute cholangitis was associated with early discharge.

Coronary orbital atherectomy using a five-French guiding catheter.

Recently, the efficacy was demonstrated of the Diamondback 360® Coronary Orbital Atherectomy System (OAS) (Cardiovascular Systems, Inc., St. Paul, MN, USA) for treating calcified coronary lesions in percutaneous coronary intervention (PCI). The safety and feasibility of OAS application through a 5-Fr guiding catheter (GC) which is less invasive and reduces access site complications were validated. This sequential, retrospective, observational study was conducted in a single center from September 2018 to May 2020. The primary endpoint was a successful PCI with the OAS. Secondary endpoints were major adverse complications related to PCI with the OAS, including coronary dissection, perforation, side branch loss, need for an unexpected cardiac assist device, access site complications, and major adverse cardiac and cerebrovascular events. 33 PCIs in 30 patients (mean age 72 ± 11 years; male, 83.3%) were surveyed. All PCIs were successfully completed with OAS application through a 5-Fr GC. Coronary perforation after the OAS procedure occurred in one case (3.0%). Severe coronary dissection occurred in three cases (9.1%), and procedural myocardial infarction in two cases (6.1%). Regarding PCIs performed with the 5-Fr GC, the OAS is a safe and feasible strategy for calcified plaque modification.