大宮 直木

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Ate+Bev) is widely used as first-line therapy for unresectable hepatocellular carcinoma (HCC). However, a subset of patients experience early disease progression, often detected at the first radiologic assessment around 6 weeks. Evidence guiding second-line therapy in this subgroup is limited, and the clinical value of lenvatinib after early progressive disease (PD) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with unresectable HCC who received lenvatinib after failure of first-line Ate+Bev. Patients were stratified by early PD, defined as radiologic progression at the scheduled 6-week assessment after starting Ate+Bev. Outcomes included antitumor response, progression-free survival (PFS), and overall survival (OS). RESULTS: Objective response rate (ORR) and disease control rate (DCR) assessed by RECIST 1.1 were comparable between patients with and without early PD (ORR: 28.6% vs. 13.8%; DCR: 85.7% vs. 86.2%; p=0.342). Median PFS was also similar between groups [5.2 months (95% confidence interval=1.9-NA) vs. 6.1 months (3.7-7.5); p=0.307]. In multivariate analyses adjusting for Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and reduced starting dose, early PD was not significantly associated with either PFS or OS, whereas Child-Pugh class A was independently associated with improved OS. Correlation between first- and second-line PFS was weak and non-significant (r=0.077, p=0.682). CONCLUSION: Lenvatinib demonstrated comparable antitumor activity and survival outcomes even in patients with early PD on first-line Ate+Bev, indicating that early radiologic progression does not necessarily signify refractoriness to subsequent systemic therapy. These findings support lenvatinib as a viable second-line option regardless of early Ate+Bev response, particularly in patients with preserved liver function. Larger prospective studies are needed to confirm these observations.

BACKGROUND: Owing to the rarity of metastatic tumors in the small bowel, their clinicopathological features, and prognostic factors remain poorly understood. This study aimed to clarify the clinicopathological features and factors associated with the prognosis of patients with small bowel metastasis from other organs in Japan. METHODS: We retrospectively examined 253 patients who were histopathologically diagnosed with small bowel metastases between January 2008 and December 2017 at multiple institutions in Japan. We identified the clinicopathological features of the condition and determined the factors associated with the prognosis of these patients. RESULTS: Obstructive symptoms were the most frequent clinical presentations (39% abdominal pain and 18% vomiting), while gastrointestinal bleeding was observed in 27% of patients. The diagnostic modalities included enteroscopy (33%), balloon-assisted enteroscopy (30%), and capsule endoscopy (13%). The most common primary tumor was lung cancer (38%), followed by colorectal cancer (18%), gastric cancer (9%), and malignant melanoma (6%). Surgical intervention, including tumor resection or bypass surgery, was performed in 79% of patients. The cumulative survival rates of patients at 12, 24, and 60 months were 49%, 36%, and 22%, respectively. Multivariate analysis identified surgery as a significant factor for improving overall survival (HR = 0.56, 95% CI 0.35-0.89, p = 0.01). CONCLUSIONS: The lung cancer is the most frequent primary tumor of metastatic tumors in the small bowel. Surgical intervention was associated with improved survival outcomes.

BACKGROUND: Peutz-Jeghers syndrome (PJS), a rare genetic disorder characterized by hamartomatous gastrointestinal polyps, poses increased risks of various cancers. Despite the importance of early intervention, the optimal timing for jejunal-ileal polypectomy remains unclear owing to the limited number of comparative studies. METHODS: Herein, we conducted a nationwide survey in Japan and analyzed data from 184 patients with PJS identified through a two-stage sampling process. The initial screening of 2912 medical institutions yielded 1748 facilities, of which 1077 responded to the survey. Time-dependent Cox proportional hazards models and logistic regression analyses were used to examine the association between the timing of jejunal-ileal polypectomy and the risk of surgery for intussusception. RESULTS: Among 184 patients (47.0% women; mean age, 33.5 years), intussusception was the most common complication (67.7%). In the Cox proportional hazards analysis excluding surgeries within 1 year of diagnosis, early jejunal-ileal polypectomy was associated with a reduced risk of surgery for intussusception (adjusted hazard ratio, 0.17; 95% confidence interval [CI] 0.04-0.74, p = 0.018). Logistic regression analysis showed higher odds of surgery in the late treatment group compared with the early treatment group (adjusted odds ratio, 4.26; 95% CI 1.38-13.16, p = 0.012). CONCLUSIONS: Early jejunal-ileal polypectomy may reduce the risk of intussusception in patients with PJS. However, the need for frequent endoscopic procedures must be balanced considering patient burden. These findings support the importance of early intervention and highlight the need for optimized surveillance strategies that consider clinical effectiveness and patients' quality of life.

BACKGROUND & AIMS: Although biologic therapy has revolutionized the treatment of Crohn's disease (CD), surgery remains unavoidable in cases involving ileal complications. We aimed to evaluate the efficacy of biologics on proximal ileal lesions using balloon-assisted enteroscopy (BAE). METHODS: This open-label multicenter prospective study was conducted at tertiary referral centers in Japan. We enrolled 253 patients with active ileal CD who were treated with biologics (infliximab/adalimumab/ustekinumab/vedolizumab). BAE was performed at week 0 and week 26, and endoscopic findings were centrally assessed. We evaluated the rate of endoscopic remission (defined as having a maximum modified Simple Endoscopic Score for Crohn's disease <4) at week 26 and patient prognosis (CD-related hospitalization and surgery). RESULTS: At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations. The second BAE showed that endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum. The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%), a trend consistently observed across all treatment agents. After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). CONCLUSIONS: A substantial proportion of patients with CD exhibited ulcerations in the proximal ileum, which correlated with a poorer prognosis. These lesions proved challenging to heal, regardless of the type of biologic used.