Total bile acids levels as a stratification tool for screening portopulmonary hypertension in patients with decompensated cirrhosis.

AIM: Echocardiography is necessary for portopulmonary hypertension diagnosis, and identifying patients with cirrhosis who require it is challenging. In this study, we aimed to investigate the utility of the total bile acid (TBA) levels as a screening tool for identifying patients with decompensated cirrhosis who should undergo echocardiography for portopulmonary hypertension diagnosis. METHODS: We evaluated 135 patients with decompensated cirrhosis who underwent liver transplantation. Subsequently, factors contributing to tricuspid regurgitation pressure gradient (TRPG) elevation (≥30 mmHg) were analyzed using preoperative data, including the TBA levels. RESULTS: The median age of patients was 58 years (61 women), and 45 and 90 patients had Child-Turcotte-Pugh grades of B and C, respectively. The median TRPG level was 21 mmHg, and 17 patients (12.6%) showed TRPG elevation. Multiple logistic regression analysis revealed that elevated TBA (odds ratio 4.322; p = 0.013) and main pulmonary artery diameter ≥33 mm (odds ratio 4.333; p = 0.016) were significantly associated with TRPG elevation. The TBA cut-off value (167.7 µmol/L) showed a high diagnostic performance, with 70.6% sensitivity and 64.4% specificity. Ursodeoxycholic acid (UDCA) administration increased the TBA levels dose-dependently. Analysis stratified by UDCA use revealed that in patients not taking UDCA (n = 59), elevated TBA levels and younger age significantly contributed to TRPG elevation. However, in those taking UDCA (n = 76), this contribution disappeared, suggesting that UDCA consumption reduced TBA levels' efficiency in diagnosing TRPG elevation. CONCLUSIONS: The TBA levels may be a potential screening tool for TRPG elevation; however, caution is warranted when interpreting cases treated with UDCA.

Alcohol-Induced Denaturation of Hen Egg White Lysozyme Studied by Infrared, Circular Dichroism, and Small-Angle Neutron Scattering.

In aqueous binary solvents with fluorinated alcohols, 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and aliphatic alcohols, ethanol (EtOH) and 2-propanol (2-PrOH), the denaturation of hen egg white lysozyme (HEWL) with increasing alcohol mole fraction xA has been investigated in a wide view from the molecular vibration to the secondary and ternary structures. Circular dichroism (CD) measurement showed that the secondary structure of α-helix content of HEWL increases on adding a small amount of the fluorinated alcohol to the aqueous solution, while the ß-sheet content decreases. On the contrary, the secondary structure does not significantly change by the addition of the aliphatic alcohols. Correspondingly, the infrared (IR) spectroscopic measurements revealed that the amide I band red-shifts on the addition of the fluorinated alcohol. However, the band remains unchanged in the aliphatic alcohol systems with increasing alcohol content. To observe the ternary structure of HEWL, small-angle neutron scattering (SANS) experiments with H/D substitution technique have been applied to the HEWL solutions. The SANS experiments were successful in revealing the details of how the geometry of the HEWL changes as a function of xA. The SANS profiles indicated the spherical structure of HEWL in all of the alcohol systems in the xA range examined. The mean radius of HEWL in the two fluorinated alcohol systems increases from ∼16 to ∼18 Å during the change in the secondary structure against the increase in the fluorinated alcohol content. On contrast, the radius does not significantly change in both aliphatic alcohol systems below xA = 0.3 but expands to ∼19 Å as the alcohol content is close to the limitation of the HEWL solubility. According to the present results, together with our knowledge of the alcohol cluster formation and the interaction of the trifluoromethyl (CF3) groups with the hydrophobic moieties of biomolecules, the effects of alcohols on the denaturation of the protein have been discussed on a molecular scale.

Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history.

BACKGROUND AND AIMS: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.

Investigation of deep learning model for predicting immune checkpoint inhibitor treatment efficacy on contrast-enhanced computed tomography images of hepatocellular carcinoma.

Although the use of immune checkpoint inhibitors (ICIs)-targeted agents for unresectable hepatocellular carcinoma (HCC) is promising, individual response variability exists. Therefore, we developed an artificial intelligence (AI)-based model to predict treatment efficacy using pre-ICIs contrast-enhanced computed tomography (CT) imaging characteristics. We evaluated the efficacy of atezolizumab and bevacizumab in 43 patients at the Nagasaki University Hospital from 2020 to 2022 using the modified Response Evaluation Criteria in Solid Tumors. A total of 197 Progressive Disease (PD), 271 Partial Response (PR), and 342 Stable Disease (SD) contrast CT images of HCC were used for training. We used ResNet-18 as the Convolutional Neural Network (CNN) model and YOLOv5, YOLOv7, YOLOv8 as the You Only Look Once (YOLO) model with precision-recall curves and class activation maps (CAMs) for diagnostic performance evaluation and model interpretation, respectively. The 3D t-distributed Stochastic Neighbor Embedding was used for image feature analysis. The YOLOv7 model demonstrated Precision 53.7%, Recall 100%, F1 score 69.8%, mAP@0.5 99.5% for PD, providing accurate and clinically versatile predictions by identifying decisive points. The ResNet-18 model had Precision 100% and Recall 100% for PD. However, the CAMs sites did not align with the tumors, suggesting the CNN model is not predicting that a given CT slice is PD, PR, or SD, but that it accurately predicts Individual Patient's CT slices. Preparing substantial training data for tumor drug effect prediction models is challenging compared to general tumor diagnosis models; hence, large-scale validation using an efficient YOLO model is warranted.

Comparison of the novel Franseen needle versus the fine-needle aspiration needle in endoscopic ultrasound-guided tissue acquisition for cancer gene panel testing: A propensity score-matching analysis.

Background and Aim: Reports have indicated that a surface area of 4 mm2 or more of collected tissue sections could provide the recommended total DNA for the OncoGuide NCC Oncopanel system, which is a cancer gene panel test developed in Japan. We wished to compare the percentage of tissue sections collected by endoscopic ultrasound-assisted tissue acquisition (EUS-TA) with surface areas of ≥4 mm2 between a conventional needle, namely the EZ Shot 3 Plus (Olympus Medical Japan, Tokyo, Japan) (EZ3), and the recent SonoTip TopGain (MediGlobe, Rohrdorf, Germany) (TopGain). Method: From April 2010 to December 2021, among 693 EUS-TA cases, EZ3 was used in 390 cases and TopGain in 45. The EZ3 and TopGain groups were matched in a 1:1 ratio with a tolerance of 0.2, with 35 patients each matched using propensity score analysis. Results: The TopGain group had a significantly higher percentage of cases with a tissue area of ≥4 mm2 than the EZ3 group (42.9% vs 68.6%, P = 0.030). Multivariate analysis revealed an association between TopGain and tissue areas of ≥4 mm2 (odds ratio 2.996, 95% confidence interval 1.068-8.403, P = 0.037). Conclusions: EUS-TA using TopGain significantly collected more ≥4 mm2 tissue area compared with EZ3, suggesting its usefulness for cancer gene panel testing.

Hypoglycemia measured by flash glucose monitoring system predicts liver-related events in chronic liver disease patients.

Impaired glucose tolerance, glucose fluctuations, and hypoglycemia have been observed in patients with chronic liver disease (CLD). The flash glucose monitoring (FGM) system, which recognises continuous and dynamic glucose changes in real time, is used in daily clinical practice. This study aimed to examine the association between glucose fluctuations and hypoglycemia, as measured by the FGM system, and liver-related events. Seventy-two patients with CLD and type 2 DM who had their blood glucose measured using Freestyle Libre Pro between April 2017 and July 2018 at our institution were enrolled in this retrospective study. We assessed the results of the FGM system measurements and liver-related events, as defined by gastrointestinal bleeding, infection, ascites, encephalopathy, and liver-related death. The standard deviation (SD) of mean glucose as measured by the FGM system was 41.55 mg/dl, and hypoglycemia was observed in 48.6% (35/72) of the patients. Liver-related event-free survival was not significant when stratified based on SD; however, the event-free survival was significantly lower when stratified by hypoglycemia (p = 0.007). In a multivariate analysis using the Cox proportional hazards model, Child-Pugh class B [Hazards ratio (HR) 2.347 (95% confidence interval (CI): 1.042-5.283), p = 0.039] and hypoglycemia [HR 2.279 (95% CI: 1.064-4.881), p = 0.034] were identified as factors contributing to event-free survival. Hypoglycemia, as determined by the FGM system, was identified as a significant factor that was closely associated with liver-related events. In addition to measuring glucose levels, the FGM system is useful in predicting the occurrence of liver-related events.

Refractory cardiac arrest caused by type I Kounis syndrome treated with adrenaline and nicorandil: A case report.

RATIONALE: Kounis syndrome is a rare but life-threatening anaphylactic reaction that can lead to acute coronary syndrome and cardiac arrest, and requires prompt diagnosis. Adrenaline, which is used to treat anaphylaxis, may cause coronary vasoconstriction and worsen ischemia, whereas coronary vasodilators may dilate systemic vessels and exacerbate hypotension. Delayed diagnosis of Kounis syndrome and inadequate therapeutic intervention may thus lead to a poor outcome. PATIENT CONCERNS: A 59-year-old man was treated for sepsis due to a liver abscess. Following administration of daptomycin, the patient developed severe anaphylactic shock leading to refractory cardiac arrest. Because conventional cardiopulmonary resuscitation was ineffective, extracorporeal cardiopulmonary resuscitation was considered as an alternative approach. DIAGNOSES: On bedside monitoring during cardiopulmonary resuscitation, unexpected ST-segment elevation was found on lead II electrocardiogram. Accordingly, the patient was clinically diagnosed with Kounis syndrome. INTERVENTIONS: Nicorandil (6 mg/h), a coronary vasodilator with minimal blood pressure effects, was administered along with high doses of vasopressors, including adrenaline 0.2 µg/kg/min. OUTCOMES: After the initiation of nicorandil administration, the patient achieved return of spontaneous circulation and did not require extracorporeal cardiopulmonary resuscitation. Based on the elevated serum tryptase level, normal creatine kinase-MB range, and lack of stenosis on coronary angiography, the patient was definitively diagnosed with type I (coronary vasospasm) Kounis syndrome. He was subsequently transferred to the referring hospital without neurological sequelae. LESSONS: If anaphylaxis leads to refractory shock and cardiac arrest, ischemic changes on the electrocardiogram should be investigated to identify underlying Kounis syndrome. In addition to adrenaline, coronary dilators are the definitive treatment. Nicorandil may be a useful treatment option because of its minimal effect on blood pressure.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Peripheral lymphocyte fluctuation as an indicator of severe immune-related adverse events in patients treated with immune checkpoint inhibitors.

AIM: Immune checkpoint inhibitors (ICIs) have proven to be effective treatments for various cancers, but can also elicit immune-related adverse events (irAEs). Given that severe irAEs can be life-threatening, biomarkers that can predict the occurrence of irAEs are of paramount importance. ICIs affect the dynamics of lymphocytes, and alterations in these dynamics may play a role in the development and severity of irAEs. The aim of this study was to investigate the correlation between irAEs and changes in lymphocyte counts. METHODS: Information on irAEs was collected from 226 ICI cases from 2014 to 2020. We compared lymphocyte counts before treatment and at the onset of irAE and investigated the association between lymphocyte count fluctuations and the presence and severity of irAE, the course after steroid treatment, and overall survival. RESULTS: Of the 226 cases, 27 patients developed grade 3 or higher irAE. Compared to the other groups, the lymphocyte count in this group was significantly decreased at the time of irAE (p < 0.01). There was a trend toward a rapid increase in lymphocyte count in the steroid responder group compared to the non-responder group. Regarding overall survival, patients with irAE had significantly longer survival than those without irAE (p = 0.0025). However, there was no association between changes in lymphocyte count and survival in patients with irAE. CONCLUSION: The percentage change in lymphocyte count was found to correlate with the incidence of severe irAEs. Close monitoring of the patient's condition is crucial when the lymphocyte count decreases during ICI treatment.

Evans' syndrome induced by atezolizumab plus bevacizumab combination therapy in advanced hepatocellular carcinoma.

An 86-year-old man presented with recurrence of hepatocellular carcinoma (HCC) after surgery. Atezolizumab plus bevacizumab was initiated. After the third course of atezolizumab plus bevacizumab therapy, petechial purpura appeared on the extremities and trunk. Laboratory tests revealed isolated severe thrombocytopenia without evidence of combined coagulopathy. He was diagnosed with immune thrombocytopenic purpura (ITP), and high-dose immunoglobulin and Helicobacter pylori eradication therapies were administered. Improvement in thrombocytopenia was observed; however, 20 days after the onset of ITP, laboratory data revealed hemolytic anemia. Both direct and indirect Coombs tests were positive, and he was diagnosed with Evan's syndrome complicated by ITP and autoimmune hemolytic anemia (AIHA) induced by immune-related adverse events (irAEs). After treatment with prednisolone, the hemoglobin level increased, and hemolytic findings improved on blood tests. We encountered a rare case of Evans' syndrome due to atezolizumab plus bevacizumab therapy for HCC. In atezolizumab plus bevacizumab therapy, hematologic toxicities are not rare adverse events and attention is required.

Five cases of endoscopically noted esophageal stenosis due to abnormal aortic angiogenesis.

Right aortic arch is caused by a malformation of the aorta while Kommerell's diverticulum is a saccular aneurysm arising at the origin of the subclavian artery. Both diseases are caused by malformations during embryonic development and can subsequently cause compression of the esophagus and trachea due to abnormal arterial migration. Here, we report five cases of esophageal stenosis due to aortic angiogenesis anomalies. Three of the five cases had aortic running abnormalities, noted on computed tomography (CT). However, until it was observed for the first time, esophageal stricture was not recognized as an esophagogastroduodenoscopy (EGD) finding due to the lack of knowledge of diseases such as Kommerell's diverticulum even when EGD was performed during regular follow-up after treatment for esophageal cancer or other conditions. Symptoms include dysphagia and dyspnea due to stenosis of the esophagus and trachea, however, regardless of symptomatic presentation, the presence of esophageal stenosis on EGD should be considered as an effect of aortic travel abnormality or Kommerell's diverticulum. Although there have been no reports of Kommerell's diverticulum rupture due to endoscopic manipulation, gastroenterologists should consider the possibility of Kommerell's diverticulum during clinical decision making.

Regular protocol liver biopsy is useful to adjust immunosuppressant dose after adult liver transplantation.

INTRODUCTION: Adjusting immunosuppression to minimal levels post-adult liver transplantation (LT) is critical; however, graft rejection has been reported in LT recipients with normal liver function evaluated by liver biopsy (LBx). Continual protocol liver biopsy (PLB) is performed regularly in LT recipients with normal liver function in some centers; however, its usefulness remains inadequately evaluated. This study aimed to assess retrospectively the usefulness of late PLB after adult LT. METHODS: LBx evaluations of LT recipients with normal liver function and hepatitis B and C virus seronegativity were defined as PLB. The cases requiring immunosuppressive therapy for rejection findings based on Banff criteria were extracted from the PLBs, and pathological data collected before and after immunosuppressive dosage adjustment (based on modified histological activity index [HAI] score) were compared. RESULTS: Among 548 LBx cases, 213 LBx in 110 recipients fulfilled the inclusion criteria for PLB. Immunosuppressive therapy after PLB was intensified in 14 LBx (6.6%) recipients (12.7%); of these, nine had late-onset acute rejection, three had isolated perivenular inflammation, one had plasma cell-rich rejection, and one had early chronic rejection. Follow-up LBx after immunosuppressive dose adjustment showed improvement in the modified HAI score grading in 10 of 14 cases (71.4%). No clinical background and blood examination data, including those from the post-LT period, immunosuppressant trough level, or examination for de novo DSA, predicted rejection in PLB. Complications of PLB were found in only three cases. CONCLUSION: PLB is useful in the management of seemingly stable LT recipients, to discover subclinical rejection and allow for appropriate immunosuppressant dose adjustment.

Most Cases of Cryptogenic Cirrhosis May Be Nonobese Nonalcoholic Steatohepatitis - Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study.

Objective The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of nonalcoholic steatohepatitis (NASH) in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m2; p=0.002) and mean muscle attenuation at the time of LT were significantly higher (33.3 vs. 25.8 Hounsfield units, p=0.03) and the postoperative hospitalization period shorter (50 vs. 102 days; p=0.02) in the steatosis group than in the non-steatosis group. Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years old; p=0.04). Conclusion Despite excluding CC patients with a history of obesity, we observed that patients with CC had a high prevalence of steatosis after LT than those without CC. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

Long-term Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. RESULTS: The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. CONCLUSION: SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

Initial and advanced endoscopic findings of monomorphic epitheliotropic intestinal T-cell lymphoma in the duodenum: A case report.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive malignant digestive system lymphoma. We report the case of a 68-year-old Asian woman who was diagnosed with MEITL of the duodenum and small intestine due to intestinal obstruction. MEITL is mainly located in the small intestine, and duodenal lesions are rare. Therefore, the endoscopic appearance of MEITL in the duodenum has been reported in only a few cases. In this case, we observed the initial and advanced endoscopic findings of MEITL in the duodenum. The initial findings were only slight mucosal changes; therefore, careful observation is required to detect early-stage MEITL.

Impact of lenvatinib on renal function compared to sorafenib for unresectable hepatocellular carcinoma.

ABSTRACT: Anti-VEGF drugs, such as tyrosine kinase inhibitors, play an important role in systemic therapy for unresectable hepatocellular carcinoma (uHCC). We examined the effects of sorafenib and lenvatinib on proteinuria and renal function.Patients who were administered sorafenib (n = 85) or lenvatinib (n = 52) as first line treatment for uHCC from July 2009 to October 2020, were enrolled in this retrospective observational study. A propensity score analysis including 13 baseline characteristics was performed. Eighty four patients were selected (sorafenib, n = 42; lenvatinib, n = 42) by propensity score matching (one-to-one nearest neighbor matching within a caliper of 0.2). We analyzed changes in estimated glomerular filtration rate (eGFR) during tyrosine kinase inhibitor treatment, as well as the development of proteinuria in both groups. A multivariate analysis was performed to identify predictors of a deterioration of eGFR.At 4, 8, 12, and 16 weeks, ΔeGFR was significantly lower in the lenvatinib group than in the sorafenib group (P < .05). The lenvatinib group showed a significantly higher frequency of proteinuria than the sorafenib group (30.9% vs 7.1%, P = .005) and had a higher rate of decrease in eGFR than the sorafenib group (P < .05). Multivariate analysis revealed that lenvatinib use was the only predictive factor of eGFR deterioration (odds ratio 2.547 [95% CI 1.028-6.315], P = .043). In cases of proteinuria ≤1+ during lenvatinib treatment, eGFR did not decrease. However, eGFR decreased in the long term (>24 weeks) in patients who have proteinuria ≥2+.Lenvatinib has a greater effect on proteinuria and renal function than sorafenib. In performing multi-molecular targeted agent sequential therapy for uHCC, proteinuria and renal function are important factors associated with drug selection after atezolizumab-bevacizumab combination therapy currently used as the first-line treatment.

Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease.

BACKGROUND: Fibrosis is the most important pathological feature in predicting development of Hepatocellular carcinoma (HCC). However, the incidence rate of HCC in patients with non-alcoholic fatty liver disease (NAFLD) is relatively low. We evaluated phenotypic histological features to differentiate HCC from non-HCC in patients with non-tumor lesions of cirrhotic livers. METHODS: Seventeen patients with NAFLD who underwent liver transplantation were enrolled. FibroNest was used to quantify histological phenotypes of non-tumor fibrosis lesions. Quantification included collagen content and structure traits, fiber morphometric traits, and fibrosis architecture traits. Each trait was described by up to seven quantitative fibrosis traits (qFTs). Among the qFTs measured in each specimen, those that described most of the variability between consecutive groups were automatically detected and combined into a normalized Phenotypic Composite Fibrosis Score (Ph-CFS). We trained FibroNest to identify the principal traits that differentiate HCC from non-HCC. RESULTS: HCC was found in 8 cases and non-HCC in 9 cases. The Ph-CFS significantly differentiated HCC from non-HCC (4.6 vs. 5.9, p < 0.05). Individual qFTs for morphometric features including collagen fiber length, width, perimeter, and area denoted significant differences between HCC and non-HCC. The Ph-CFS could be used to distinguish HCC (Ph-FCS < 5.0) from non-HCC (Ph-FCS ≥ 5.0) with 75% sensitivity and 100% specificity. CONCLUSION: In patients who underwent liver transplantation, fibrotic histological phenotypes in non-tumor lesions appeared to be different between HCC and non-HCC. Phenotypic analysis of collagen in non-tumor lesions might be an effective and automated method to distinguish HCC from non-HCC on histopathology imaging.

The Outcome of Conversion Liver Resection Surgery by Lenvatinib Treatment: A Single Center Experience.

BACKGROUND: The efficacy of molecular-targeted agents (MTAs) has been demonstrated in recent years. However, the results of multidisciplinary treatment including hepatic resection are still unclear. The present study evaluated the outcomes of MTA treatment for advanced, unresectable hepatocellular carcinoma (HCC), with the goal of achieving liver resection, in our department. PATIENTS AND METHODS: Nine patients in whom Lenvatinib had been administered to achieve conversion surgery for unresectable HCC were included in this study. The patient characteristics were as following: median tumor size of 10 cm, vascular invasion in 5 cases, multiple tumors in 2 cases, median treatment duration of 8 weeks, dose reduction due to side effects in 4 patients, and discontinuation of treatment in 1 patient due to tumor growth. RESULTS: The efficacy by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was partial response in 3, sustained disease in 5 and progressive disease in 1, while the liver resection rate was 88%. Four patients (50%) had recurrence after resection, and the median recurrence-free survival was 12.7 months; however, treatment for recurrence was successful and all patients are alive. CONCLUSION: Lenvatinib may improve the prognosis of HCC with vascular invasion and multiple lesions by achieving radical resection at the appropriate time for patients with tumor shrinkage.

Evaluating the Role of Hepatobiliary Phase of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Predicting Treatment Impact of Lenvatinib and Atezolizumab plus Bevacizumab on Unresectable Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab therapy has high response rates in patients with unresectable hepatocellular carcinoma (HCC). The hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) has been reported to be useful as an imaging biomarker for detecting ß-catenin mutations. We evaluated whether the pretreatment of the hepatobiliary phase of EOB-MRI could predict the therapeutic effect of lenvatinib and atezolizumab plus bevacizumab. METHODS: This study included 68 patients (lenvatinib group (n = 33) and atezolizumab plus bevacizumab group (n = 35)). The visual assessment and relative enhancement ratio (RER) of the largest HCC lesions were evaluated using the hepatobiliary phase of EOB-MRI. RESULTS: The hyperintensity type (RER ≥ 0.9) was 18.2% in the lenvatinib group and 20.0% in the atezolizumab plus bevacizumab group. In the lenvatinib group, progression-free survival (PFS) was not different between the heterogeneous and homogenous types (p = 0.688) or between the hyperintensity and hypointensity types (p = 0.757). In the atezolizumab plus bevacizumab group, the heterogeneous type had significantly shorter PFS than the homogenous type (p = 0.007), and the hyperintensity type had significantly shorter PFS than the hypointensity type (p = 0.012). CONCLUSIONS: The hepatobiliary phase of EOB-MRI was useful for predicting the therapeutic effect of atezolizumab plus bevacizumab therapy on unresectable HCC.