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. 2026 Jun 29;13:1835187. doi: 10.3389/fsurg.2026.1835187

Intraoperative irreversible electroporation for margin accentuation in locally advanced intrahepatic cholangiocarcinoma: a case series

Martin Brichard 1,*, Claude Bertrand 1, Quentin Gilliaux 2, Bruno Krug 3, Hadrien Fourneau 4, Claude Schalbar 5, Alexandra Dili 1
PMCID: PMC13358192  PMID: 42445467

Abstract

Introduction

The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide and remains associated with a poor prognosis. Surgical resection is the only potentially curative treatment; however, only a minority of patients are eligible due to advanced disease and vascular involvement. Irreversible electroporation (IRE) is a non-thermal ablative modality that enables tissue treatment while preserving vascular structures. This study aimed to evaluate the feasibility, safety, and preliminary oncologic outcomes of intraoperative IRE as an adjunct for margin accentuation in locally advanced iCCA involving critical vascular structures.

Methods

Between 2023 and 2024, three patients with initially unresectable, centrally located mass-forming iCCA were treated at a single center. All tumors involved the hepatic vein of the future liver remnant, precluding conventional R0 resection. Patients underwent extended hepatectomy combined with intraoperative IRE applied at the tumor–hepatic vein interface, followed by vascular detachment to preserve venous outflow.

Results

All procedures were completed as planned. No intraoperative complications or IRE-related postoperative adverse events were observed. Ninety-day mortality was 0%. Postoperative imaging confirmed preserved hepatic vein patency in all patients. At a median follow-up of 18 months (range 15–27), no local recurrence at the vascular interface was detected. One patient with initially multifocal disease developed a solitary intrahepatic recurrence at 17 months, which was successfully treated with local ablation. All patients were alive at last follow-up.

Conclusions

Intraoperative IRE for margin accentuation appears to be a feasible and safe adjunct to extended hepatectomy in selected patients with locally advanced iCCA involving the hepatic vein of the future liver remnant. This anatomy-preserving strategy may expand surgical indications by enabling radical resection in cases otherwise deemed unresectable. Further studies are required to validate its oncologic benefit.

Keywords: hepatic vein, intrahepatic cholangiocarcinoma, irreversible electroporation, liver resection, locally advanced, margin accentuation, vascular involvement

Introduction

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy after hepatocellular carcinoma. Its incidence is steadily increasing worldwide, with a parallel rise in mortality (1–3). Most patients lack identifiable risk factors, limiting opportunities for surveillance, and despite advances in systemic therapy, prognosis remains poor (3, 4). Without treatment, median overall survival (OS) is approximately 5 months (5), while first-line gemcitabine–cisplatin extends median OS to only 17 months (6). The aggressive biology and relative chemoresistance of iCCA underscore the need for more effective multimodal treatment strategies (7).

Surgical resection remains the only potentially curative treatment, achieving 5-year OS rates of 30%–40% in selected patients (8–11). However, only 20%–30% of patients present with upfront resectable disease due to locally advanced or metastatic tumor burden (8, 10). Even after R0 resection, recurrence rates exceed 60%, and only a minority of patients are eligible for repeat local treatment (12).

Achieving negative surgical margins (R0) is a key determinant of long-term survival, particularly in node-negative disease (13). However, tumors involving major vascular structures, especially the hepatic veins of the future liver remnant, pose a major surgical challenge. In this setting, conventional resection may be infeasible or associated with a high risk of R1 margins. Recent data suggest that R1-vascular resections are associated with inferior oncologic outcomes, highlighting the need for strategies that improve local control at critical vascular interfaces (14).

Irreversible electroporation (IRE) is a non-thermal ablative technique that delivers high-voltage electrical pulses to induce permanent cell membrane permeabilization, triggering multiple spatially distinct modes of programmed cell death. Cell death within the ablation zone is heterogeneous: necrosis predominates adjacent to the electrodes, while necroptosis, pyroptosis, and apoptosis occur at increasing distances from the electrode interface, with apoptosis representing a peripheral rather than a dominant central mechanism (15–17). Unlike thermal ablation, IRE preserves the structural integrity of adjacent vessels and bile ducts, making it particularly suitable for tumors in proximity to major vascular structures (18, 19). Initially developed for locally advanced pancreatic cancer, IRE has demonstrated safety and feasibility in primary and secondary liver tumors (20–25). In pancreatic surgery, its intraoperative use for margin accentuation has been associated with acceptable morbidity and no procedure-related mortality (26–28).

Despite growing interest in IRE for hepatobiliary malignancies, published experience specifically in iCCA remains extremely limited. A recent systematic review and meta-analysis of IRE for hepatic tumors included 300 patients across nine studies, yet only 21 had iCCA, and no iCCA-specific subgroup analysis was performed (29). The most relevant prospective feasibility data come from Belfiore et al., who evaluated IRE in 15 patients with unresectable cholangiocarcinoma (8 iCCA and 7 perihilar) reporting no major complications and a mean overall survival of 18 months for the combined cohort; however, outcomes were not reported separately by tumor location, limiting conclusions specific to iCCA (23). Most remaining series either aggregate intrahepatic and perihilar cases without subgroup analysis or focus exclusively on perihilar disease, and recent reviews have consistently highlighted the paucity of iCCA-specific data as a critical gap in the field (30). Critically, no prior study has evaluated IRE as an intraoperative margin accentuation strategy in resectable iCCA with vascular involvement.

Given these properties and the absence of dedicated clinical data, IRE represents a particularly attractive adjunct in iCCA with vascular involvement, where achieving negative margins remains technically challenging.

The aim of this study was to report our initial experience with intraoperative IRE for margin accentuation in patients with locally advanced iCCA involving the hepatic vein of the future liver remnant. To our knowledge, this represents the first clinical series evaluating this approach.

Materials and methods

Study design

This retrospective study was conducted using a prospectively maintained clinical database.

Ethics

The study protocol was approved by the institutional Ethics Committee (approval no. 120/2025). All procedures were performed in accordance with the Declaration of Helsinki. Written informed consent for surgery and data collection was obtained from all patients.

Patients

Between 2023 and 2024, three consecutive patients with locally advanced intrahepatic cholangiocarcinoma (iCCA) with multisectoral hepatic involvement precluding conventional surgical resection, underwent radical liver resection combined with intraoperative irreversible electroporation (IRE) for margin accentuation at a single tertiary hepatopancreatobiliary (HPB) center. Patient demographics and baseline characteristics are summarized in Table 1.

Table 1.

Baseline clinical and tumor characteristics of the three patients.

Variable Patient 1 Patient 2 Patient 3
Tumor characteristics
 Tumor size (mm) 110 112 60
 Location IV-V-VIII + II + III I-II-III-IV-VIII I-II-IV-VIII
 Number of nodules 3 1 1
 Vascular contact RHV RHV RHV
 Contact length (mm) 34 22 25
 Circumferential involvment (°) 90−180 < 90 90–180
 Growth pattern Mass forming Mass forming Mass forming
 CA 19-9 (kU/L) 39.4 7.4 95.0
 cTNM cT2N0M0 cT1bN0M0 cT1bN0M0
 Neoadjuvant therapy Cisplatin-Gemcitabine-Durvalumab+SIRT - Cisplatin-Gemcitabine-Durvalumab
Liver characteristics
 UNDERLYING LIVER DISEASE Steatosis Steatosis Steatosis
 FLR (segment) VI-VII V-VI-VII V-VI-VII
 FLR pre (%) 36 55 48
 HBS FLRF pre (%/min/m²) 1.9 3.6 2.7
 FLR MODULATION TECHNIQUE SIRT - -
 FLR post (%) 58 - -
 HBS FLRF post (%/min/m²) 2.5 - -

RHV, right hepatic vein; SIRT, selective internal radiation therapy; FLR, future liver remnant; HBS FLRF, hepatobiliary scintigraphy FLR function.

All cases were discussed in a multidisciplinary team (MDT) setting. Tumors were considered locally advanced due to involvement of all three hepatic veins, including the hepatic vein draining the future liver remnant (FLR), precluding conventional R0 resection (Figure 1). Histological confirmation of iCCA was obtained in all patients. Tumor characteristics, including size, morphological subtype, and preoperative staging, are detailed in Table 1.

Figure 1.

Pre-operative CT scan showing tumor contact with the right hepatic vein in patient 1 and 3. Vascular involvement is not visible in pre-operative CT scan for patient 2, and only found during intra-operative ultrasonography.

Pre-operative CT scan showing tumor contact with the right hepatic vein (white arrow) in patient 1 (A) and 3 (B). Vascular involvement not visible in pre-operative CT scan for patient 2 (C) only found during intra-operative ultrasonography (D).

Preoperative staging included triple-phase thoracoabdominal computed tomography (CT). Additional imaging with positron emission tomography (PET)-CT and/or contrast-enhanced magnetic resonance imaging (MRI) was performed when indicated. The degree of hepatic vein involvement was assessed on preoperative cross-sectional imaging (CT and/or MRI) and characterized by two parameters: the length of tumor-hepatic vein contact (mm) and the degree of circumferential involvement, classified as less than 90°, 90–180°, or greater than 180°. These parameters are reported individually for each patient in Table 1.

FLR adequacy was assessed using functional evaluation combining volumetric analysis with 99mTc-mebrofenin hepatobiliary scintigraphy. A threshold of 2.3%/min/m² was used to define sufficient FLR function (FLRF) (31). Preoperative volumetric and functional liver data are reported in Table 1.

Two patients received neoadjuvant therapy consisting of chemo-immunotherapy, combined with selective internal radiotherapy (SIRT) in one case, for tumor downstaging and contralateral hypertrophy of the FLR. Both patients demonstrated radiological response or stable disease by RECIST criteria, however persistent hepatic vein involvement of the FLR remained. The indication for intraoperative IRE margin accentuation was determined by MDT when contralateral hepatic vein involvement was identified on preoperative imaging.

No alternative curative strategy was deemed feasible by the MDT: vascular reconstruction was considered unsuitable due to the extent of vascular involvement (>5 cm), and liver transplantation remains investigational in this setting. A vascular detachment approach combined with intraoperative irreversible electroporation for margin accentuation was therefore preferred.

Surgical procedure

All procedures were performed by a senior HPB surgeon (AD).

Exploratory laparoscopy with intraoperative ultrasonography (IOUS) was systematically performed to exclude peritoneal or intrahepatic metastases prior to resection. Regional lymphadenectomy was carried out routinely, including frozen-section analysis of para-aortic lymph nodes (station 16) to exclude metastatic disease before proceeding with hepatectomy. Lymphadenectomy of the hepatoduodenal ligament (station 12) and common hepatic artery nodes (station 8) was subsequently completed.

IRE was performed in situ under IOUS guidance prior to parenchymal transection to ensure accurate needle positioning. The procedure was carried out jointly by two surgeons (AD and MB).

Parenchymal transection was then carried out under IOUS guidance, using a Cavitron Ultrasonic Surgical Aspirator (CUSA; Valleylab, Boulder, CO, USA) with intermittent pedicle clamping. Hepatic vein detachment was achieved using a combination of CUSA and blunt dissection. Vessels >2 mm were ligated with titanium clips or 3-0 sutures, and bipolar coagulation was used for hemostasis of the transection surface.

IRE procedure

IRE was performed using the NanoKnife system (AngioDynamics, Latham, NY, USA).

Under intraoperative ultrasound (IOUS) guidance, two to three electrodes were positioned in a linear configuration along the tumor–hepatic vein interface to achieve targeted electroporation of the vascular margin (Figure 2). The active tip length was 15 mm, and inter-electrode spacing ranged from 15 to 20 mm, adjusted according to local tumor anatomy. Individual electrode number and spacing for each patient are detailed in Table 2.

Figure 2.

3D medical illustration showing liver tumor and its relation to portal vein and hepatic vein as well as needle placement alongside the hepatic vein - tumor interface.

Top view (A) and right lateral view (B) of the liver showing tumor (green) contact with both hepatic veins (blue) and left portal pedicle (purple), as well as IRE needle placement (yellow). 3D rendering was generated using 3D Slicer (version 5.8.1, http://www.slicer.org/) with the RVXLiverSegmentation plugin.

Table 2.

Perioperative outcomes of the three patients undergoing radical hepatectomy with IRE margin accentuation.

Variable Patient 1 Patient 2 Patient 3
Surgery
 Hepatectomy Left extended hepatectomy Left hepatectomy extended to segment VIII with bile duct resection Left hepatectomy extended to segment VIII
 “New World” terminology H123458 + IRE-MA H12348-B-MHV + IRE-MA H12348-MHV + IRE-MA
 IRE needles number 3 2 2
 IRE needles spacing (mm) 15 20 20
 Intraoperative adverse event Yes (RHV hemorrhage/hepatotomy) No No
 Duration of surgery (min) 660 675 420
 Pringle time (min) 10 35 20
 Estimated blood loss (ml) 2,500 1,200 600
Morbi-mortality
 Morbidity (Clavien-Dindo) IIIA II II
 Ascitis Yes No No
 Bile leak No No No
 Post-hepatectomy hemorrhage No No No
 PHLF (ISGLS grade) No No No
 Intra-abdominal infection Yes No No
 Other complications - Delayed gastric emptying Sectorial portal vein thrombosis Anemia Pleural effusion
 ICU stay (days) 3 3 1
 Hospital saty (days) 22 24 11
 90-day mortality No No No

IRE-MA, irreversible electroporation for margin accentuation; RHV, right hepatic vein; PHLF, post-hepatectomy liver failure; ISGLS, international study group of liver surgery; ICU, intensive care unit.

A total of 100 pulses per electrode pair were delivered at 1,500 V/cm (±300 V/cm), targeting a current of 30–40 A. The first 20 pulses were used to assess tissue conductivity, followed by 80 therapeutic pulses, in accordance with the manufacturer's protocol.

Procedural adequacy was monitored intraoperatively through continuous real-time display of delivered current by the NanoKnife generator. Amperage trends were used as a qualitative indicator of electroporation-induced tissue conductivity changes; however, given the absence of a validated current rise threshold for hepatobiliary tumors, no fixed amperage criterion was applied as a binary endpoint for procedural success (32, 33).

For larger lesions, a “pull-back” technique was used, consisting of partial electrode withdrawal followed by a second treatment cycle to ensure coverage of the superficial tumor interface.

All patients underwent cardiac synchronization using a five-lead ECG gating system to ensure pulse delivery during the cardiac refractory period and prevent arrhythmias.

Follow up

Postoperative management followed institutional standards. Complications were recorded prospectively and graded according to the Clavien–Dindo (CD) classification and International Study Group of Liver Surgery (ISGLS) definitions (34, 35).

Patients were followed at 1 month postoperatively and every 3 months thereafter.

Adjuvant therapy consisted of capecitabine followed by chemoradiotherapy when tolerated.

Outcomes

Clinical, perioperative, and oncological data were extracted from the institutional database.

Collected variables included patient demographics, tumor characteristics, neoadjuvant treatment, operative details, IRE parameters, histopathological findings, postoperative outcomes (morbidity, length of stay, 90-day mortality), recurrence patterns, and survival.

Disease-free survival (DFS) was defined as the interval from surgery to first radiologically confirmed recurrence. Overall survival (OS) was defined as the time from surgery to death from any cause or last follow-up.

Results

Peri-operative outcomes

The first patient underwent SIRT prior to surgery for tumor downstaging and to induce contralateral liver hypertrophy, given a low future liver remnant function (FLRF) of 1.9%/min/m² and the associated high risk of post-hepatectomy liver failure (PHLF). Four months after SIRT and completion of neoadjuvant therapy, FLRF increased to 2.5%/min/m². The patient subsequently underwent left extended hepatectomy [H123458 according to the “New World” terminology (36)] with IRE margin accentuation along the right hepatic vein interface. Intraoperative bleeding from the distal right hepatic vein occurred during parenchymal transection and was controlled without sequelae. No IRE-related adverse events were observed.

The second patient underwent left hepatectomy extended to segment VIII with bile duct resection. As the tumor was initially considered resectable, no neoadjuvant therapy was administered. IOUS revealed involvement of the hepatic vein of the future liver remnant (Figure 1D), prompting intraoperative IRE margin accentuation at the right hepatic vein interface. The procedure was uneventful.

The third patient underwent left hepatectomy extended to segment VIII following neoadjuvant therapy, with IRE margin accentuation at the right hepatic vein interface. No intraoperative complications occurred.

Overall, one patient developed a major complication (Clavien–Dindo ≥ III), consisting of an intra-abdominal abscess originating from the liver section surface, treated successfully by percutaneous drainage. This complication was spatially distinct from the IRE ablation zone: IRE was performed exclusively at the hepatic vein interface and was not applied to the parenchymal section margin as a whole, which remained outside the electroporation field. No vascular complications were observed in any patient, with preserved hepatic vein patency confirmed on post-operative imaging in all cases. No patients developed PHLF, post-hepatectomy hemorrhage, bile leak, or hepatic vein thrombosis (Figure 3). 90-day mortality was 0%. Detailed perioperative characteristics are summarized in Table 2.

Figure 3.

Post-operative CT scan of patient 1 and patient 2 at post-operative day 7 showing good patency of right hepatic vein.

Post-operative CT scan of patient 1 (A) and patient 2 (B) at POD 7 showing good patency of right hepatic vein (white arrow).

Oncological outcomes

All specimens demonstrated microscopically positive margins (<1 mm) at the hepatic vein interface on final pathology.

All patients received adjuvant chemotherapy with capecitabine, followed by radiotherapy (54 Gy) to the surgical margin when clinically feasible.

One patient, initially presenting with multifocal intrahepatic disease, developed a solitary metachronous intrahepatic recurrence 17 months after surgery. This lesion was treated with microwave ablation, and the patient remains disease-free 10 months after treatment of recurrence.

No local recurrence at the hepatic vein interface was observed. All patients were alive at last follow-up (range 15–27 months). Detailed oncological outcomes are presented in Table 3.

Table 3.

Pathological and oncological outcomes of the three patients undergoing radical hepatectomy with IRE margin accentuation.

Variable Patient 1 Patient 2 Patient 3
Pathology
 pTNM ypT2N0 pT2N0 ypT1bN0
 Lymphadenectomy (nodes) 8 30 23
 Microvascular invasion No Yes No
 Perineural invasion No Yes No
 Resection margin R1-vascular (RHV contact) R1-vascular (RHV contact) R1-vascular (RHV contact)
Adjuvant therapy
 Chemotherapy Capecitabine Capecitabine Capecitabine
 Radiotherapy 54 Gy 54 Gy No
Follow up
 OS (months) 27 18 15
 DFS (months) 17 18 15
 Local recurrence (liver margin) No No No
 Intrahepatic recurrence Yes No No
 Extrahepatic recurrence No No No

RHV, right hepatic vein; OS, overall survival; DFS, disease-free survival.

Discussion

Intrahepatic cholangiocarcinoma (iCCA) remains a highly aggressive malignancy with limited curative options. Although surgical resection is the cornerstone of treatment, long-term outcomes remain suboptimal, with 5-year OS rarely exceeding 30%–40% and recurrence rates reaching up to 70%, predominantly within the liver and frequently at or near the resection margin (37, 38). These patterns underscore the critical role of achieving adequate local disease control.

Margin status is consistently identified as one of the strongest prognostic factors in iCCA. Institutional series have reported local recurrence rates of 45%–50% after R1 resection vs. approximately 10% after R0 resection, confirming the oncologic disadvantage associated with microscopic residual disease (13). In a large multicenter cohort in which R1 was defined as ≤1 mm, overall recurrence reached approximately 65%, and R1 resection independently increased the risk of recurrence compared with R0 resection (HR 1.6) (37). Among those who recurred, 53% developed intrahepatic-only recurrence, and 24% recurred specifically at or near the surgical margin. Recurrence patterns were markedly early: 62% recurred within 12 months, and 83% within 24 months of surgery. Notably, approximately half of all margin recurrences were detected within 6 months of surgery (37). These figures underscore that the surgical margin represents a critical site of early treatment failure in iCCA, highlighting the importance of strategies aimed at improving local control in this anatomical region.

However, the surgical management of tumors involving major vascular structures, especially the hepatic vein of the future liver remnant, remains particularly challenging. In such cases, conventional R0 resection is often not feasible, and the disease is frequently deemed unresectable (14).

To overcome these limitations, increasingly aggressive surgical strategies have been developed, including vascular reconstruction, R1-vascular resections, and in highly selected cases liver transplantation. Selected series have reported encouraging outcomes, particularly in node-negative patients undergoing complex vascular procedures (11). However, these approaches are associated with increased operative complexity and morbidity, especially in cases requiring reconstruction of the last remaining hepatic vein, often necessitating extended resections, prolonged operative time, and significant blood loss (39–43).

More recently, the concept of R1-vascular resection has challenged the traditional paradigm that all R1 margins are oncologically equivalent. First described by Torzilli et al. the R1-vascular approach involves careful detachment of the tumor from major intrahepatic vessels along the Laennec capsule plane. The oncological adequacy of this approach has been previously demonstrated in both colorectal liver metastases and hepatocellular carcinoma (44–46). Milana et al. reported comparable rates of local recurrence between R0 and R1-vascular resections (16% vs. 10%). In contrast, R1-parenchymatous resection was associated with a markedly higher rate of local recurrence compared to R0 (45% vs. 10%). These findings suggest that the Laennec capsule may act as a natural barrier to tumor spread, and that vascular-adjacent margins may behave differently from true parenchymal R1 disease (39). Nevertheless, disease-free survival remains inferior in these patients (3-year DFS 11% vs. 34%), suggesting that while vascular detachment may preserve local control at the margin itself, it does not fully mitigate the overall risk of disease recurrence. This limitation highlights the potential role of adjunctive strategies such as IRE to further consolidate tumor control at the vascular interface.

Liver transplantation has recently emerged as a potential option in highly selected patients with locally advanced iCCA following successful downstaging (41, 47). However, its applicability remains limited due to strict selection criteria, donor organ scarcity, and high dropout rates. In contrast, strategies that expand resectability while preserving native liver anatomy remain broadly applicable and may benefit a larger patient population.

In parallel, multimodal strategies incorporating systemic therapy, immunotherapy, and liver-directed treatments such as selective internal radiation therapy (SIRT) have expanded the pool of patients eligible for curative-intent approaches (48–52). These modalities may enable downstaging and improve patient selection; however, they do not fully address the technical challenge of achieving adequate margins when tumors involve critical vascular structures (53). Furthermore, radiological assessment after neoadjuvant therapy remains imperfect, particularly in distinguishing fibrosis from viable tumor at vascular interfaces (54).

In this context, intraoperative irreversible electroporation (IRE) offers a complementary, anatomy-preserving approach. By inducing non-thermal cell death while preserving vascular and biliary structures, IRE enables targeted treatment of microscopic disease at sites where surgical clearance is limited. Rather than replacing resection, IRE may function as a margin-accentuation tool, specifically addressing the vascular interface where conventional techniques are either unsafe or insufficient.

This concept has been explored in other malignancies, particularly pancreatic cancer, where IRE-based margin accentuation has been associated with improved local control despite advanced disease stage and acceptable morbidity (28, 55). The IRE protocol used in this series is consistent with established NanoKnife parameters validated in preclinical porcine liver models, with expected ablation zone dimensions of approximately 2.0–2.5 cm in width and 2.5–3.0 cm in height per electrode pair position, as derived from published in vivo data (56, 57). Whether these findings translate to the hepatic setting remains uncertain. The anatomical context of iCCA with hepatic vein involvement differs substantially from the pancreatic resection margin. IRE at the hepatic vein interface benefits from the vessel's inherent resistance to electroporation-induced injury, which is less applicable at the pancreatic margin. Against this background, our study explores whether this approach may be extended to iCCA, a setting in which vascular proximity frequently limits resectability.

In the present series, intraoperative IRE was safely integrated into complex liver surgery, with no IRE-related complications, no vascular thrombosis, and preserved hepatic vein patency in all cases. These findings confirm the technical feasibility of applying IRE along major hepatic veins without compromising vascular integrity (18, 19).

Although all patients had microscopically positive margins at the hepatic vein interface, no local recurrence was observed during follow-up. This observation supports the hypothesis that IRE may achieve effective in situ tumor control that is not immediately reflected in histopathological assessment, likely due to its delayed programmed cell death mechanisms, including necroptosis, pyroptosis, and apoptosis (16, 18).

Nevertheless, these findings must be interpreted with caution. The small sample size, single-center design, and limited follow-up preclude definitive conclusions regarding oncologic benefit. Furthermore, as detailed in the Introduction, published experience with IRE specifically in iCCA remains extremely limited, with no prior study evaluating its intraoperative use for margin accentuation in the resectable setting, a knowledge gap that precludes meaningful benchmarking of our findings against historical IRE efficacy data in this disease. In addition, the incremental value of IRE over contemporary R1-vascular strategies remains uncertain, particularly in light of recent data suggesting comparable local control between R0 and R1-vascular resections (39).

Despite these limitations, this study provides the first clinical evidence that intraoperative IRE can be safely used as an adjunct to liver resection for margin accentuation in iCCA. This approach may represent a novel strategy to expand surgical indications in patients with tumors involving critical vascular structures, particularly when conventional resection or reconstruction is not feasible.

Further prospective studies are warranted to better define the oncologic impact of this strategy and to identify the patients most likely to benefit from its application.

Conclusion

To our knowledge, this is the first case series reporting the use of intraoperative IRE for margin accentuation in locally advanced iCCA.

In this preliminary experience, intraoperative IRE was feasible and safe when applied at the hepatic vein interface, without compromising vascular integrity. This anatomy-preserving approach may facilitate radical resection in selected patients with vascular involvement of the future liver remnant who would otherwise be considered unresectable.

Although limited by the small sample size and short follow-up, these findings support further investigation of IRE as an adjunct to liver resection within a multimodal treatment strategy. Larger prospective studies are required to define its oncologic benefit and to clarify its role in relation to vascular reconstruction and R1-vascular resection.

Funding Statement

The author(s) declared that financial support was not received for this work and/or its publication.

Footnotes

Edited by: Gabriel Sandblom, Karolinska Institutet (KI), Sweden

Reviewed by: Altamura Amedeo, Pia Fondazione di Culto e Religione Card. G. Panico, Italy

Yujue Wang, Sichuan University, China

Thomas An, Massachusetts General Hospital and Harvard Medical School, United States

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

The studies involving humans were approved by the institutional Ethics Committee. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

MB: Conceptualization, Data curation, Methodology, Visualization, Writing – original draft, Writing – review & editing. CB: Supervision, Visualization, Writing – review & editing. QG: Writing – review & editing. BK: Writing – review & editing. HF: Writing – review & editing. CS: Writing – review & editing. AD: Conceptualization, Supervision, Visualization, Writing – review & editing.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was used in the creation of this manuscript. During the preparation of this work the authors used ChatGPT (GPT5, OpenAI) in order to to improve readability and English language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

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Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.


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