Saiseikai Niigata Daini Hospital

Background/AimSystemic therapy with immune checkpoint inhibitors for advanced hepatocellular carcinoma (HCC) treatment has demonstrated high response rates. Durvalumab plus tremelimumab (Dur/Tre) has been approved for HCC treatment and has become a first-line systemic therapy along with atezolizumab plus bevacizumab. However, there is early withdrawal owing to immune-related adverse effects, while others required sequential therapy owing to the lack of early therapeutic effects. Herein, we investigated the clinical characteristics of patients with progressive disease (PD) who were treated with Dur/Tre in addition to locoregional therapy.Patients and MethodsWe retrospectively evaluated eight patients with HCC, who were treated with Dur/Tre in March 2025 and continued Dur/Tre until PD was treated with locoregional therapy. Additionally, immunological changes, and treatment efficacy during continuation therapy were also assessed. Treatment efficacy was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST).ResultsAt Dur/Tre induction, patients (mean age, 76.88 years, all male) had alcoholic liver disease (n=3), nonalcoholic steatohepatitis (n=4), or hepatitis B virus (n=1). Six patients received Dur/Tre as first-line therapy, two were treated with atezolizumab plus bevacizumab as pretreatment, and the mean number of Dur/Tre cycles was 5.2. Neutrophil to lymphocyte ratio (NLR) was 2.14±1.51 at the time of Dur/Tre induction and worsened to 2.80±1.91 at the time of PD but significantly improved to 2.08±1.14 after locoregional therapy (p=0.047). Des-gamma-carboxy prothrombin (DCP) levels also decreased significantly after locoregional therapy (p=0.021). One patient responded partially, and seven achieved disease stability with continued treatment.ConclusionContinued Dur/Tre therapy may be effective in patients with improved NLR and DCP levels after adjunct locoregional therapy. Further studies involving larger patient cohort might determine strategic addition of locoregional therapy in PD.

This study aimed to elucidate the morphological and proliferative progression of dysplasia in sessile serrated lesions (SSLs) to submucosal invasive carcinoma (SIC). Seventy-six SSLs with dysplasia, including 20 with SIC, were analysed. Each lesion was systematically partitioned into morphological units (MUs) based on cytological atypia (low/high) and gland pattern (serrated/tubular), resulting in 200 MUs: serrated-low (n = 76), serrated-high (n = 34), tubular-low (n = 26), and tubular-high (n = 64). These MUs were further categorised as SIC-related (n = 21) or -unrelated (n = 179). Ki67 immunostaining defined proliferative zones within each MU: lower (Ki67-L, n = 70), upper (Ki67-U, n = 40), diffuse (Ki67-D, n = 58), and other (n = 32, excluded from statistical analyses). Fisher's exact test was used in the following specific analyses.Significant associations between serrated-low MUs and SIC-unrelated MUs, and between tubular-high MUs and SIC-related MUs (p < 0.001, respectively) were observed. Moreover, Ki67-L patterns were absent in SIC-related MUs (0/70, 0%, p < 0.001), predominantly in serrated-low MUs (45/70, 64%, p < 0.001). Conversely, Ki67-D patterns were enriched in SIC-related (20/58, 34%, p < 0.001) and tubular-high MUs (39/58, 67%, p < 0.001). Furthermore, Ki67-U patterns exhibited intermediate frequencies between Ki67-L and Ki67-D patterns, with one (2.5%) in SIC-related MUs, six (15%) in serrated-low MUs, and 16 (40%) in tubular-high MUs. This study revealed a significant correlation between Ki67 expression patterns and morphological progression of dysplasia in SSLs. Additionally, the observed Ki67 redistribution, from lower to upper mucosa, followed by diffuse downward spread, mirrors the top-down growth pattern observed in conventional adenomas. Further molecular studies focusing on these proliferative zones are crucial for elucidating the underlying mechanisms of dysplasia progression in SSLs.

Background/Objective: Recently, there has been an increasing need to implement the diagnosis of the presence of covert hepatic encephalopathy (CHE) in patients with cirrhosis. The aim of this study was to identify novel factors associated with CHE in clinical practice. Methods: This retrospective study enrolled a total of 402 patients with cirrhosis at 17 institutions. The Stroop test was performed to diagnose CHE at each center. Results: The patients comprised 233 males and 169 females, with a median age of 69 (IQR, 61-75) years. The median albumin and 25(OH)D3 levels were 3.9 (3.5-4.3) g/dL and 15.4 (11.0-21.0) ng/mL, respectively. This cohort included 181 patients with esophageal varices (EV). Multivariate analysis revealed that low 25(OH)D3 (p < 0.05) and EV (p < 0.05) were independent risk factors for CHE. When limited to only laboratory factors, low albumin (p < 0.01) and low 25(OH)D3 (p < 0.05) were independent factors for CHE. The optimal cut-off values of albumin and 25(OH)D3 for predicting CHE were 3.7 g/dL and 16.5 ng/mL, respectively. The prevalence of CHE was 59.2% for 25(OH)D3 < 16.5 ng/mL and EV, 53.8% for albumin < 3.7 g/dL and 25(OH)D3 < 16.5 ng/mL, and 66.7% for albumin < 3.7 g/dL, EV, and 25(OH)D3 < 16.5 ng/mL. Conclusions: Low 25(OH)D3 and albumin levels, and the EV were positively associated with CHE in patients with cirrhosis. Specifically, the prevalence of CHE increased with a decrease in 25(OH)D3 levels. Patients with such risk factors should be actively and carefully examined for the presence of CHE.

The link between lifestyle-related conditions and fatty liver disease has attracted considerable attention in recent years. The number of patients with metabolic dysfunction-associated steatotic liver disease (MASLD), often co-occurring with obesity, diabetes, and dyslipidemia, continues to rise. Accumulating evidence suggests that these conditions synergistically increase the risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Consequently, there is a growing need for testing to identify high-risk liver disease patients based on lifestylerelated conditions, distinct from chronic viral hepatitis or alcohol-induced liver disease, and to determine the most appropriate treatments for these conditions, especially obesity, diabetes, and dyslipidemia. This review outlines the strategy for treating fatty liver disease currently being used in community hospitals, with the goal of reducing HCC and preventing cardiovascular disease.

Although transarterial chemo-embolization (TACE) is a key treatment for hepatocellular carcinoma (HCC), its effectiveness depends on the cannulation of the microcatheter tip into the feeding artery. Steerable microcatheters allow remote operation of the tip, enabling its insertion into feeding arteries otherwise difficult to reach. This study investigated the indications and effectiveness of steerable microcatheters in TACE for HCC. We retrospectively examined 22 patients with HCC who underwent TACE using steerable microcatheters at our Department between December 2014 and July 2024. Previous TACE administration, number of TACE sessions, and feeding artery disruption affecting TACE were examined. Among the first TACE cases requiring steerable catheters, three demonstrated steep bifurcation of the celiac artery or superior mesenteric artery from the parent artery, two had sharp bends in the posterior segment, and four had the left hepatic artery bifurcating from the left gastric artery. All three procedures performed in the inferior phrenic artery required second TACE sessions. Steerable microcatheters were used in two patients during their eighth TACE session; both procedures involved selective cannulation of neovessels feeding from a new anastomotic branch to segment 4, following damage to the main feeding artery from repeated treatments. Steerable microcatheters were effective in reaching steep or strongly bending branches of the parent or feeding artery in the first TACE cases or neovessels and anastomotic branches in previous TACE cases. Studies with larger sample sizes are warranted to validate the use of steerable microcatheters for effective TACE.

Imatinib therapy is the gold standard for the treatment of unresectable and metastatic gastrointestinal stromal tumors (GISTs). However, few studies have reported the long-term outcomes of the treatment. Seventy patients who underwent imatinib therapy for unresectable and metastatic GISTs were enrolled between 2001 and 2009, and follow-up data were collected until October 2023. One hundred and sixty-eight months had passed since the final enrollment. The outcome measures were patient survival and the status of GIST and imatinib therapy. The cumulative incidence of disease progression (PD) and the chronological changes in PD hazard rate (HR) were also analyzed. The 5-, 10-, 15-, and 20-year overall survival rates were 64.3%, 30.0%, 16.8%, and 12.2%, respectively. Sixty of the 70 enrolled patients died before the data cutoff date: 47 (78.3%) patients died of GIST progression while the remaining 13 (21.7%) died of diseases other than GISTs. The cumulative incidence of PD logarithmically increased, and PD continued even after 10years of treatment. PD HR decreased over time to reach the lowest value at 9.6years after the initiation of treatment (HR 0.00027; 95% CI 0.00007-0.00174) and after that formed a small peak at 13years (HR 0.00144; 95% CI 0.00043-0.00436). Imatinib therapy showed high clinical efficacy in terms of long-term survival in GIST patients. However, patients undergoing imatinib therapy were at continuous risk of PD even after the 10-year treatment. Long-term treatment and follow-up beyond 10years are necessary for unresectable and metastatic GIST patients.

Total knee arthroplasty (TKA), which has medial pivot and mobile-bearing mechanisms, has been developed and clinically used. However, the in vivo dynamic kinematics of the mobile medial pivot-type TKA (MMPTKA) is unclear. This study analysed the in vivo kinematics of MMPTKA in weight-bearing and nonweight-bearing conditions. The study included 10 knees that underwent primary TKA using MMPTKA. After TKA, lateral view radiographs of the knee in full extension, 90° of flexionand passive full flexion were taken under general anaesthesia in the nonweight-bearing condition. At least 6 months postoperatively, knee motion during squatting from a weight-bearing standing position was observed using a flat-panel detector and analysed using the three-dimensional-to-two-dimensional image registration technique. Under anaesthesia: in passive full flexion, the anteroposterior (AP) locations of the femoral component's medial and lateral distal points were 10.2 and 16.0 mm posterior, and the rotational angles of the femoral component's X-axis (FCX) and insert were 8.1° external rotation and 18.5° internal rotation to full extension, respectively. Squatting: the AP translations of the femoral component's medial and lateral most distal points were 2.2 and 6.4 mm, and the rotational angles of the FCX and insert were 5.7° and 1.6° external rotation, respectively. Significant differences were observed in the AP translation of the femoral component's medial and lateral most distal points and changes in the insert's rotational angle when comparing under anaesthesia and squatting. The kinematics of the insert in MMPTKA was significantly influenced by loading and muscle contraction. The femoral component exhibited substantial external rotation and posterior translation under anaesthesia, which may contribute to achieving an optimal range of motion. The insert remained relatively stable during squatting and minimal rotation was observed, indicating good stability. MMPTKA was expected to demonstrate rational kinematics by incorporating mobile and medial pivot mechanisms. Level IV,prospective biomechanical case series study.