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With recent advances in chemotherapy for unresectable pancreatic ductal adenocarcinoma (PDAC) with liver metastasis (LM), attempts have been made to resect the primary tumor in patients showing favorable responses to anti-cancer treatment (so-called “conversion surgery”; CS). This study aimed to clarify the outcomes of CS for PDAC with LM in a nationwide multicenter study. This retrospective, multicenter study was conducted as a project study of the Japan Pancreas Society and included patients with PDAC with LM at initial diagnosis, diagnosed radiologically or intraoperatively (occult LM), who underwent CS after at least 4 months of chemotherapy between 2010 and 2022. Survival outcomes and prognostic factors were analyzed. 90 patients were enrolled from 31 Japanese institutions. Median duration of preoperative chemotherapy was 10.4 (range, 4.2–58.5) months, and gemcitabine plus nab-paclitaxel was the most common first-line regimen, followed by folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin. Liver metastasectomy was performed in 27 patients (30
Abstract We analyzed the impact of the diagnosis-to-treatment interval (DTI) on survival in patients with CD5-positive diffuse large B-cell lymphoma (CD5 + DLBCL), using a data set of newly diagnosed patients. Among the 336 eligible patients, 247 (74%) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), and 89 (26%) were treated with dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The median DTI was 18 days (range 0–118). The short DTI (≤ 14 days) group included 135 patients (40%), and the long DTI (> 14 days) group included 201 patients (60%). Compared with the long DTI group, the short DTI group had more aggressive disease characteristics. Both the progression-free survival (PFS) (P = 0.01) and the overall survival (OS) (P < 0.01) were significantly inferior in the short DTI group compared with those in the long DTI group. Among 89 patients who received DA-EPOCH-R, no significant differences in PFS (P = 0.92) or OS (P = 0.86) were observed between the two groups. Multivariate analysis revealed that no DA-EPOCH-R was a risk factor for PFS in the short DTI group (P = 0.06). A short DTI was a negative prognostic factor in our CD5 + DLBCL cohort. DA-EPOCH-R could be considered a potential treatment option for patients with a short DTI.
BackgroundHepatitis B virus (HBV) infection remains a leading cause of hepatocellular carcinoma (HCC), yet the molecular mechanisms underlying HBV-mediated hepatocarcinogenesis are not fully understood. This study focused on miR-4461, which is encoded within the intronic region of PCBD2 gene, and investigated its role in HBV-derived HCC.MethodsmiR-4461 expression was examined in HBV-expressing hepatoma cell lines and in HBV-infected primary human hepatocytes. Functional analysis evaluated the effects of miR-4461 overexpression or inhibition on hepatocyte proliferation. Candidate targets were screened, and fibrinogen alpha chain (FGA) was tested for regulation by miR-4461. Circulating miR-4461 and plasma FGA were measured in patients with chronic viral hepatitis, including those with HBV-related HCC; in the HBV-HCC cohort, FGA was also assessed before and after surgical tumor resection.ResultsmiR-4461 expression was significantly reduced in HBV-expressing hepatoma cells and HBV-infected primary hepatocytes. Overexpression of miR-4461 inhibited hepatocyte proliferation, whereas its inhibition enhanced proliferation, indicating a tumor-suppressive function. FGA was identified as a downstream target; in hepatoma cells, FGA protein levels were regulated by miR-4461. Clinically, circulating miR-4461 levels were significantly lower in HBV-infected individuals, particularly in those with HBV-related HCC. In contrast, plasma FGA protein levels were markedly elevated in HBV-related HCC and decreased significantly after tumor resection.ConclusionsThese findings suggest a novel regulatory axis in HBV-associated HCC involving HBV-induced suppression of miR-4461 and subsequent upregulation of FGA. Both miR-4461 and FGA were associated with disease status, supporting their potential utility as biomarkers or therapeutic targets in HBV-derived HCC.
Anastomotic leakage most frequently occurs within the first postoperative week, when intrinsic tissue strength is limited. Although bioabsorbable reinforcement materials are widely used, the optimal degradation profile remains unclear. This study evaluated whether short-term bioabsorbable reinforcement improves early mechanical stability compared with medium-term reinforcement in a controlled porcine small bowel model. Ten pigs underwent laparotomy, and three standardized jejunal end-to-end anastomoses were created in each animal: control, short-term reinforcement, and medium-term reinforcement. Animals were sacrificed at 1 week (n = 5) or 3 weeks (n = 5). The primary endpoint was intraluminal bursting pressure, and rupture location was recorded. At 1 week, bursting pressures were 87 (72–98) mmHg in controls, 156 (136–182) mmHg in the medium-term group, and > 200 mmHg in the short-term group (p < 0.001). Both reinforcement groups exceeded controls, and short-term reinforcement showed the highest strength. All specimens ruptured at the anastomotic line. At 3 weeks, all groups exceeded the measurement limit (> 200 mmHg); however, rupture location differed significantly, with controls failing at the suture line and reinforced segments rupturing away from the anastomosis (p < 0.01). Histology demonstrated increased subanastomotic connective tissue thickness in reinforced groups, particularly at 1 week. Short-term bioabsorbable reinforcement markedly enhanced early mechanical stability and altered late rupture patterns, suggesting restoration of structural competence. Temporal alignment between degradation and early healing may represent a rational strategy to improve anastomotic outcomes.
Abstract Introduction Tumor-draining lymph nodes (LNs) are critical for initiating and maintaining antitumor immunity. However, systematic LN dissection (LND) remains the standard surgical procedure for lung cancer. This study aimed to investigate the immunological impact of tumor-draining LND on systemic T cell subsets. Methods We prospectively analyzed perioperative peripheral blood and resected LN samples from patients with early-stage lung adenocarcinoma who underwent lobectomy with systematic LND (systematic LND group) or wedge resection without LND (LN-preserving group). Perioperative immune cell dynamics were comprehensively profiled using mass cytometry. Results Unlike conventional CD4+ and CD8+ T cell subsets, Th7R (CXCR3±CCR4−CCR6+ CD62LlowCD4+ T cell), a Th1-like CD4+ T cell cluster essential for antitumor immunity, consistently decreased in peripheral blood after tumor resection in both groups (p = 0.0016 and p = 0.0033). This decline was significantly milder in the LN-preserving group than in the systematic LND group (p = 0.0153). In LN analyses, Th7R percentages were significantly higher in hilar, interlobar, and peripheral LNs than in subcarinal and other mediastinal LNs (p = 0.0148). Th7R percentages in resected LNs strongly and negatively correlated with postoperative changes in peripheral blood (r = −0.857, p = 0.0137). Furthermore, greater declines in Th7R in peripheral blood were associated with postoperative oncological disease events. Conclusions Preserving LNs contributes to maintaining systemic antitumor immunity after surgery for early-stage lung cancer. Hilar, interlobar, and peripheral LNs may serve as primary reservoirs and supply sources of Th7R. In early-stage disease, these findings suggest a potential immunological benefit of LN-preserving strategies.
