Yusuke Wakasa

Perineural invasion (PNI) is a frequent pathological feature of distal cholangiocarcinoma. The spatial molecular programs associated with PNI are unclear. We aimed to characterize tumor–nerve–immune interactions linked to PNI using spatial transcriptomics and independent validation. Spatial transcriptomics was performed using GeoMx Digital Spatial Profiler on six cases of surgically resected distal cholangiocarcinoma (non‐PNI, n = 3; PNI, n = 3). Regions of interest included non‐PNI tumor regions, surface mucosal tumor regions without neural contact (PNI‐surface), and tumor regions adjacent to S100‐positive nerves (PNI‐perineural). Tumor compartments were enriched by CK19‐based segmentation. Differential expression and pathway analyses were performed using iDEP/DESeq2 and Reactome/Kyoto Encyclopedia of Genes and Genomes enrichment. Validation at the protein level was conducted using immunohistochemistry in an independent cohort (non‐PNI, n = 22 and PNI, n = 82) for nerve growth factor (NGF), CD68, and CD163. Three‐dimensional nerve architecture was assessed in nine additional cases using tissue clearing. PNI‐associated compartments and non‐PNI regions had distinct transcriptional profiles. Compared to that in non‐PNI, 109 genes were differentially expressed in PNI‐surface (34 up‐ and 75 downregulated) and 179 in PNI‐perineural (64 up‐ and 115 downregulated). Pathway analyses identified enrichment of immune‐, microenvironment‐, and neurotrophic‐related programs, including NGF‐associated signatures. Tumor‐cell NGF expression was significantly higher in PNI‐positive tumors (median H ‐score: 215 versus 119, p < 0.0001) and increased with depth in PNI cases ( p < 0.0001). Deep invasive regions of PNI‐positive tumors saw a significant increase in CD68‐positive (median 313 versus 210 cells per high‐power field, p < 0.001) and CD163‐positive (median 64 versus 40 cells per high‐power field, p < 0.01) macrophages. CD163/CD68 ratio increased in deep versus surface regions, specifically in PNI‐positive tumors ( p < 0.0001). PNI‐positive distal cholangiocarcinoma exhibited spatially distinct tumor programs and depth‐dependent remodeling involving NGF upregulation and M2‐like macrophage enrichment, identifying potential therapeutic targets. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Background: Endoscopic treatment of postoperative biliary strictures in patients with surgically altered anatomy can be technically challenging. The Drill Dilator advances by rotational torque with minimal forward pushing, potentially facilitating dilation while maintaining endoscope stability. This study evaluated the feasibility and safety of the Drill Dilator as an initial dilation device for postoperative biliary strictures in patients with surgically altered anatomy. Methods: We retrospectively reviewed 46 endoscopic sessions for postoperative biliary strictures performed between December 2016 and April 2026. Among these, 18 initial treatment sessions were included in the comparative analysis. Six sessions in which the Drill Dilator was used as the initial dilation device were evaluated and compared with 12 sessions using conventional dilation devices. Results: The Drill Dilator successfully passed and dilated the stricture in all sessions (100%). Additional dilation with another device was required in 50% of sessions (3/6). Technical success was achieved in all sessions (100%). Mild post-ERCP cholangitis (PEC) occurred in two patients (33.3%), with no severe procedure-related adverse events. In the conventional dilation group, device passage and technical success rates were 100% (12/12) and 91.7% (11/12), respectively. Conclusions: The Drill Dilator was feasible as an initial dilation device for postoperative biliary strictures in patients with surgically altered anatomy. Its use may facilitate subsequent endoscopic dilation, particularly in situations where alignment between the dilation device and the bile duct is challenging.

Introduction: In recent years, the practical application of remote robotic surgery has become a reality, and is expected to be applied to difficult surgeries. The purpose of this study is to demonstrate whether the pancreaticojejunostomy in a pancreaticoduodenectomy, a difficult surgery, can be performed through a remote surgery‐assisted robotic operation, as well as to verify the feasibility of remote surgery‐assisted pancreaticojejunostomy. Methods: Hirosaki city and Goshogawara city (about 30 km) were connected via a commercial communication line using the hinotori surgical robot, and five surgeons performed remote surgery on an artificial organ model for pancreaticojejunostomy. Four local surgeons were instructed remotely. Each procedure was repeated 3–5 times in sets of 8 min, and communication latency, Image Quality Score, System Usability Scale (mSUS), and Robot Usability Score were all evaluated. Results: The communication latency was stable at less than 12 msec, and there were no problems in performing the surgery. No significant differences were noted in Image Quality Score, System Usability Scale (mSUS), or Robot Usability Score. Pancreaticojejunostomy was performed using the Blumgart anastomosis technique, and all procedures were completed without any issues. Conclusion: We demonstrated that pancreaticojejunostomy can be performed in a telesurgical environment. This system can be applied to remote surgical guidance and support in the future and it is expected to correct regional disparities in medical care, improve surgical education, and enhance the implementation of remote surgery in society.

Assuring communication redundancy during the interruption and establishing appropriate teaching environments for local surgeons are essential to making robotic telesurgery mainstream. This study analyzes robotic telesurgery with telementoring using standard domestic telecommunication carriers. Can multiple carriers guarantee redundancy with interruptions? Three commercial optical fiber lines connected Hirosaki University and Mutsu General Hospitals, 150 km apart. Using Riverfield, Inc. equipment, Hirosaki had a cockpit, while both Mutsu used both a cockpit and a surgeon’s console. Experts provided telementoring evaluating 14 trainees, using objective indices for operation time and errors. Subjective questionnaires addressed image quality and surgical operability. Eighteen participants performed telesurgery using combined lines from two/three telecommunication carriers. Manipulation: over 30 min, lines were cut and restored every three minutes per task. Subjects were to press a switch when noticing image quality or operability changes. Mean time to task completion was 1510 (1186–1960) seconds: local surgeons alone and 1600 (1152–2296) seconds for those under remote instructor supervision, including expert intervention time. There was no significant difference (p = 0.86). The mean error count was 0.92 (0–3) for local surgeons and 0.42 (0–2) with remote instructors. Image quality and operability questionnaires found no significant differences. Results communication companies A, B, and C: the A/B combination incurred 0.17 (0–1) presses of the environment change switch, B/C had 0, and C/A received 0.67 (0–3), showing no significant difference among provider combinations. Combining multiple communication lines guarantees communication redundancy and enables robotic telementoring with enhanced communication security.

Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of β-catenin-activated inflammatory hepatocellular adenoma with malignant transformation. A 50-year-old man with a suspected liver tumor, based on abdominal ultrasonography findings, was referred to our hospital. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a liver tumor in S2 which was enhanced in the arterial phase to the delayed phase. Based on diagnostic imaging findings, hepatocellular adenoma or focal nodular hyperplasia was suspected. We considered the possibility of malignant potential because of the enlargement of the lesion. Thus, we performed a laparoscopic hepatectomy. Histological examination showed pigment deposition in the hepatocytes, which was determined to be lipofuscin. Mild nuclear swelling and atypia in the tumor area indicated nodular growth. Based on the histological and immunohistochemical findings, the diagnosis was ꞵ-catenin-activated inflammatory hepatocellular adenoma with atypical features. The imaging features of hepatocellular adenoma and focal nodular hyperplasia are similar, but if the tumor tends to grow, surgical treatment should be performed because of the possibility of malignant hepatocellular adenoma.

Purpose: Failure and recurrence are concerns in nonoperative management (NOM) for acute appendicitis (AA) and interval appendectomy (IA). The goal of the study was to identify predictors of failure and recurrence in patients with AA who underwent NOM. Methods: A total of 348 adults with appendicitis were treated in our department from April 2016 to October 2021. Among these patients, 337 who did not undergo emergency surgery were divided into those for whom NOM was unsuccessful, leading to unplanned surgery (n=28) and those successful with NOM (n=309). These groups were compared to identify predictive factors for NOM failure. In the NOM-success group, 195 patients were further subdivided into non-recurrence (n=166) and recurrence (n=29) groups to identify predictive factors for recurrence of appendicitis. Results: In multivariate analysis, posttreatment CRP level [odds ratio (OR) = 1.126, 95% confidence interval (CI) 1.076-1.179, P < 0.001] and fecal stones with abscess formation (OR=5.530, 95% CI 2.081-14.691, P=0.001) were independently associated with NOM failure. Receiver operating characteristic curve analysis showed an optimum cutoff CRP level of 10.46 mg/dl for appendicitis treatment failure. The initial CRP level was significantly lower and the percent drop of CRP was significantly higher in the recurrence group than in the nonrecurrence group. Conclusions: These findings suggest that the posttreatment CRP level and fecal stones with abscess formation are predictors for NOM failure, but that recurrence may not be affected by the severity of previous bouts of appendicitis.

Background: Conversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer. Case presentation: A 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis. She underwent gemcitabine plus cisplatin therapy for 9 months. Extended cholecystectomy, resection of the extrahepatic bile duct with regional lymph node dissection, and total omentectomy were then performed as conversion surgery. The patient has survived without recurrence for 19 months postoperatively (31 months after the initial diagnosis) while continuing chemotherapy. Conclusions: This case suggests that conversion surgery for advanced gallbladder cancer is effective and may be curative for locally advanced disease and distant metastasis such as peritoneal carcinomatosis.