Takahiro Nishio

Pancreas–intestine composite transplantation (PITx) is a therapeutic option for patients with irreversible loss of both pancreatic and intestinal function. We report a case of PITx in a 16‐year‐old male who developed fulminant Type 1 diabetes mellitus complicated by non‐occlusive mesenteric ischemia, resulting in extensive intestinal necrosis. Despite intensive surgical and critical care management, the patient ultimately required total small intestinal resection and total pancreatectomy. After recovery from sepsis and multiorgan dysfunction, the patient's general condition stabilized, and PITx was considered an appropriate therapeutic option. The composite graft consisted of the pancreas, duodenum, small intestine, and right colon. Arterial inflow was reconstructed using a single Carrel patch incorporating the celiac axis and superior mesenteric artery, and venous outflow was established by portal vein anastomosis. Postoperatively, pancreatic endocrine function was restored, allowing stable glycemic control without exogenous insulin, and intestinal graft function enabled the gradual advancement of enteral and oral nutrition. This report highlights the key technical considerations and anatomical principles of PITx and demonstrates that tailored composite graft transplantation can restore both pancreatic and intestinal function while preserving unaffected abdominal organs in highly selected patients with combined pancreatic and intestinal failure.

Purpose: This study aimed to investigate the prognostic impact of the interval between curative‐intent local treatments in patients undergoing repeated therapies for recurrent hepatocellular carcinoma after hepatectomy. Methods: The present retrospective cohort study included 890 patients who underwent hepatectomy for HCC at our hospital between 2001 and 2020. Overall survival (OS) was evaluated from the time of each curative‐intent local treatment, according to the number of treatments received and the intervals between consecutive curative‐intent treatments for intrahepatic recurrence, up to the fourth session. Results: During follow‐up, 625 patients (65.9%) developed intrahepatic recurrence. The median intervals gradually shortened to 24.9, 14.5, 12.4, and 12.8 months from hepatectomy to the first curative treatment, from the first to the second, from the second to the third, and from the third to the fourth treatments, respectively. For the first and second curative treatments, the pretreatment interval was not an independent predictor of OS. At the third curative treatment, an interval < 18.6 months between the second and third curative treatments independently predicted poorer OS (hazard ratio [HR] 2.280 and 95% confidence interval [CI] 1.046–4.967). For the fourth curative treatment, an interval < 14.1 months between the third and fourth treatments was an independent adverse prognostic factor (HR 4.961, 95% CI 1.607–15.319). The prognostic impact of treatment interval was more pronounced in patients who underwent ≥ 3 treatments, with a significant interaction compared with < 3 treatments. Conclusions: Among patients who remained eligible for repeated curative‐intent local treatment, a shortened interval between treatments in late‐phase recurrence was an independent predictor of poor prognosis.

Background: Cancer-associated fibroblasts (CAFs) represent a predominant cell population in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). How the spatial distribution of CAF subtypes relates to immune modulation within the TME remains incompletely understood. This study aimed to characterize the spatial organization of CAF subtypes in HCC and to explore their potential associations with immune contexture. Methods: Spatial transcriptomic analysis was performed on 6 HCC cases to identify CAF-enriched clusters and their spatial localization. Immunohistochemical analyses were conducted on 132 HCC sections to examine the relationship between CAF-related features, immune cell distribution, and clinical outcomes. Results: Spatial transcriptomic analysis identified distinct CAF sub-clusters, including myofibroblastic CAFs (myCAFs), which were predominantly localized within tumor regions and enriched for extracellular matrix–related gene expression; inflammatory CAFs (iCAFs), which were preferentially localized within tumor septa and associated with inflammatory signaling; and antigen-presenting CAFs (apCAFs), which were enriched in the peritumoral zone and exhibited gene expression patterns suggestive of immune-related functions. Interactome analysis suggested that apCAFs in the peritumoral region showed transcriptional patterns consistent with CXCL12–CXCR4–related interactions with CD8 ⁺ T cells accumulating at the tumor periphery. The enrichment of apCAFs on the outer side of tumor septa was associated with reduced intra-tumoral CD8 ⁺ T-cell infiltration and poorer prognosis, suggesting a link between apCAF distribution and an immune-excluded TME. Conclusions: Spatial transcriptomic profiling suggests that CAFs exhibit functional and spatial polarization in the TME of HCC. ApCAFs are associated with CXCR4-related immune exclusion at the tumor–stroma interface and may represent a stromal component relevant to immune modulation. These findings provide a framework for CAF–immune interactions and serve as a basis for future functional studies targeting the CXCL12–CXCR4 axis.

Background: Post‐hepatectomy liver failure (PHLF) is traditionally considered a transient perioperative complication with limited long‐term consequences, yet its long‐term oncologic implications in hepatocellular carcinoma (HCC) remain unclear. Methods: Patients undergoing primary hepatectomy for HCC between 2007 and 2018 were analyzed. To ensure reliable assessment of recurrence and post‐recurrence survival, follow‐up was continued through 2023. Associations between PHLF and overall survival (OS), time to recurrence (TTR), and survival after recurrence (SAR) were assessed. Propensity score matching (PSM) analysis controlled for baseline differences. Results: PHLF ≥ grade B occurred in 59 patients (14.6%). It was significantly associated with worse OS (45.6 vs. 109.7 months, p < 0.001) and SAR (21.5 vs. 55.9 months, p < 0.001), but not TTR. After PSM, these associations persisted. At recurrence, patients with PHLF had worse ALBI scores (−1.92 vs. –2.57, p < 0.001) and lower rates of re‐resection for recurrent disease (6.9% vs. 29.3%, p = 0.026), even after PSM. Conclusions: PHLF ≥ grade B compromised hepatic reserve at recurrence and limiting curative salvage therapy, leading to impaired SAR and OS. Prevention of PHLF should be prioritized not only to reduce perioperative risk but also to optimize long‐term oncologic outcomes in HCC.

Robotic hepatectomy using the Hugo robotic‐assisted surgery (RAS) system has recently been introduced; however, clinical experience remains limited. We report our initial experience in five patients, focusing on surgical techniques and short‐term outcomes. All procedures were completed robotically without conversion to open or laparoscopic surgery. The median operative time was 175 min (range, 162–209), and the median console time was 100 min (range, 79–139). The median inflow occlusion time was 31 min (range, 14–62). Intraoperative blood loss was minimal, with a median of 0 mL (range, 0–10). No intraoperative or postoperative complications were observed. The median postoperative hospital stay was 7 days (range, 4–11). The series included lesions in both left‐ and right‐sided liver segments, including technically demanding areas such as segment 7. These findings suggest that Hugo RAS minor hepatectomy appears feasible and safe in selected cases, with favorable short‐term outcomes.

Background: Multidisciplinary treatment of hepatocellular carcinoma (HCC) has made notable advancements with the emergence of novel agents for systemic therapies, including receptor tyrosine kinase inhibitors (TKIs) and cancer immuno-oncology therapy (IO) utilizing immune checkpoint inhibitors. Although each of these regimens is effective as monotherapy for advanced HCCs, combining them with local treatments (LRT), such as transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and radiotherapy (RT), provides an additional antitumor effect. The emergence of novel systemic therapies has given rise to anticipation for the development of multidisciplinary treatments with a combination of systemic therapy and LRT, which aim to achieve curative-intent resection and improve long-term prognosis after resection. Summary: Perioperative combination therapy, a combination of multiple treatment modalities including systemic therapy (TKI and/or IO) and LRT (TACE, HAIC, or RT), is attracting attention as a potentially useful approach for multidisciplinary curative-intent surgical resection or ablation. Currently, there is no evidence-based guidance regarding selection criteria and optimal regimens for perioperative combination therapy. The definition of oncological resectability for HCC is being pursued to establish the indication and protocol for perioperative combination therapy, which broadly encompasses conversion as well as neoadjuvant and adjuvant therapy for intermediate-to-advanced HCC. Key Messages: Perioperative combination therapy, which positions curative-intent surgical resection or ablation within the combination of multiple modalities including systemic therapy and LRT, provides perspectives for improving the long-term prognosis of patients with initially unresectable HCC and borderline resectable HCC with a high risk of recurrence.

Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy‐related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child–Pugh score and model for end‐stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin‐bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc‐99m‐labeled galactosyl serum albumin scintigraphy and gadolinium‐enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF.